TETRASUBSTITUTED BENZENES
This application claims priority to U.S. provisional application Ser. No. 61/015,605, filed Dec. 20, 2007, and to U.S. provisional application Ser. No. 61/109,665, filed Oct. 30, 2008, both of which are herein incorporated by reference. Alzheimer's disease (AD) is the most prevalent form of dementia. It is a neurodegenerative disorder that is associated (though not exclusively) with aging. The disorder is clinically characterized by a progressive loss of memory, cognition, reasoning and judgment that leads to an extreme mental deterioration and ultimately death. The disorder is pathologically characterized by the deposition of extracellular plaques and the presence of neurofibrillary tangles. These plaques are considered to play an important role in the pathogenesis of the disease. These plaques mainly comprise of fibrillar aggregates of β-amyloid peptide (Aβ), which are products of the amyloid precursor protein (APP), a 695 amino-acid protein. APP is initially processed by β-secretase forming a secreted peptide and a membrane bound C99 fragment. The C99 fragment is subsequently processed by the proteolytic activity of γ-secretase. Multiple sites of proteolysis on the C99 fragment lead to the production of a range of smaller peptides (Aβ 37-42 amino acids). N-terminal truncations can also be found e.g. Aβ (4-42, 11-42) for convenience Aβ40 and Aβ42 as used herein incorporates these N-terminal truncated peptides. Upon secretion, the Aβ peptides initially form soluble aggregates which ultimately lead to the formation of insoluble deposits and plaques. Aβ42 is believed to be the most neurotoxic, the shorter peptides have less propensity to aggregate and form plaques. The Aβ plaques in the brain are also associated with cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, multi infarct dementia, dementia pugilistisca, inclusion body myositis and Down's Syndrome. γ-secretase is an association of four proteins: Aph1, Nicastrin, Presenillin and Pen-2 (review De Strooper 2003, Neuron 38, 9). Aβ42 is selectively increased in patients carrying particular mutations in one of these components, presenilin. These mutations are correlated with early onset a familial AD. Inhibition of γ-secretase resulting in the lowering of Aβ42 is a desirable activity for the pharmaceutical community and numerous inhibitors have been found, e.g., Thompson et al (Bio. Org. and Med. Chem. Letters 2006, 16, 2357-63), Shaw et al (Bio. Org. and Med. Chem. Letters 2006, 17, 511-16) and Asberom et al (Bio. Org. and Med. Chem. Letters 2007, 15, 2219-2223). Inhibition of γ-secretase though is not without side-effects, some of which are due to the γ-secretase complex processing substrates other than C99, for e.g. Notch. A more desirable approach is to modulate the proteolytic activity of the γ-secretase complex in a manner that lowers Aβ42 in favor of shorter peptides without significantly affecting the activity of γ-secretase on substrates such as Notch. Compounds that have shown modulation of γ-secretase include certain non-steroidal, anti-inflammatory drugs (NSAIDs), for example Flurbiprofen, (Stock et al Bio. Org. and Med. Chem. Letters 2006, 16, 2219-2223). Other publications that disclose agents said to reduce Aβ42 through the modulation of γ-secretase include: WO 04/074232, WO 05/054193, Perreto et al Journal of Medicinal Chemistry 2005, 48 5705-20, WO05/108362, WO 06/008558, WO 06/021441, WO 06/041874, WO 06/045554, WO04110350, WO 06/043964, WO 05/115990, EP1847524, WO 07/116,228, WO 07/110,667, WO 07/124,394, EP184752, EP 01849762, WO 07/125,364. Described herein are tetrasubstituted benzene compounds of formulas (I) and (II) and pharmaceutically acceptable salts thereof A is CO2H or tetrazole;
and wherein each alkyl or cycloalkyl of R1 and R2 is optionally independently substituted with one or more halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl, provided that both R1 and R2 are not H, or
(a) C1-C6 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O), or —S(O)2— groups, (b) (C3-C7)cycloalkyl, (c) (C0-C3)alkyl-(C3-C7)cycloalkyl, (d) heterocycloalkylalky and (e) (CH2)nQ wherein n=0-2 and wherein Q is a mono- or bicyclic aromatic or heteroaromatic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, and wherein Q is optionally independently substituted with up to 3 groups selected from alkyl, halogen, CF3, OH, OCF3, alkoxy, OCH2CH2OCH3, NH2, alkylamino, dialkylamino, morpholino, CN, NO2, alkylthio and alkylsulfonyl; R7 is independently chosen from alkyl, alkoxyethyl, cycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl or (CH2)nQ, wherein n=0-2 and wherein Q is a mono or bicyclic aromatic or heteroaromatic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C and wherein Q is optionally substituted with up to 3 groups independently selected from alkyl, halogen, CF3, OH, OCF3, alkoxy, OCH2CH2OCH3, NH2, alkylamino, dialkylamino, morpholino, CN, NO2, alkylthio, alkylsulfonyl; or in the case when two R7 are attached to the same N and are both alkyl, they can be taken together to form a 5-membered or 6-membered ring optionally containing O, S, N(H) or N-alkyl;
(b) (C0-C3)alkyl-(C3-C7)cycloalkyl, (c) heterocycloalkylalkyl, or (d) a group Z, wherein Z is a mono- or bi-cyclic ring system having 3 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. In the case where R3 is a mono- or bi-cyclic ring system having 5 to 10 ring atoms, the attachment site may be either at a carbon atom or a nitrogen atom of the mono- or bi-cyclic ring system provided that only three bonds are made to nitrogen; R4 is a (a) C1-C7 alkyl group optionally and independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (b) (C0-C3)alkyl-(C3-C7)cycloalkyl, (c) heterocycloalkylalkyl or (d) a group Z, wherein Z is a mono- or bi-cyclic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. In the case where R4 is a mono- or bi-cyclic ring system having 5 to 10 ring atoms, the attachment site may be either at a carbon atom or a nitrogen atom of the mono- or bi-cyclic ring system provided that only three bonds are made to nitrogen; and R5 is selected from: NO2, NH2, aryl, heteroaryl, F, Cl, Br, CN, OH, C1-C4 alkoxy, SR6, S(O)2R6, S(O)2N(R7)2, (C1-C4) alkyl, (C0-C3)alkyl-(C3-C7) cycloalkyl, —O—(C0-C3)alkyl-(C3-C7)cycloalkyl, and (C2-C4) alkynyl, wherein each alkyl or cycloalkyl is optionally independently substituted with one or more halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl
In one embodiment R1 and R2 are taken together form a 3-7 membered cycloalkyl or heterocycloalkyl ring. In another embodiment R1 is hydrogen and R2 is F, R6, OH, OR6, SR6, NHR7, N(R7)2 NHC(O)R6, NHCO2R6 wherein R6 and R7 are as defined previously. In a further embodiment R1 is hydrogen and R2 is R6, OR6 or SR6. In an additional embodiment R1 is hydrogen and R2 is alkyl, alkoxy or thioalkyl. In another embodiment R1 is hydrogen and R2 is R6. In a further embodiment R1 is hydrogen and R2 is C1-C4 alkyl. In one embodiment X is a bond. In another embodiment X is a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S—, —CH2SCH2—, —C(O)NH—, —C(O)N(R7)—, —NHC(O)—, —N(R7)C(O)—, —S(O)—, —S(O2)—, S(O)2N(H)—, —S(O)2N(R7)—, —N(H)S(O)2—, —N(R7)S(O)2— wherein the point of attachment of divalent linking groups, X, to R3 in the Formulas I and II is to the right. In another embodiment X is —O—, —OCH2—, —OCH(R7)—, CH2O—, —S—, —S(O)2—, —S(O)2N(H)—, —S(O)2N(R7)—, —C(O)NH— or —C(O)N(R7)—. In a further embodiment X is —O—, —S(O)2—, —S(O)2N(H)— or —S(O)2N(R7)—. In another embodiment X is —O— or —S(O)2—. In one embodiment Y is a bond. In another embodiment Y is a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S—, —CH2SCH2—, —C(O)NH—, —C(O)N(R7)—, —NHC(O)—, —N(R7)C(O)—, —S(O)—, —S(O2)—, —S(O)2N(H)—, —S(O)2N(R7)—, —N(H)S(O)2—, —N(R7)S(O)2— wherein the point of attachment of divalent linking groups, X, to R3 in the Formulas I and II is to the right. In another embodiment Y is —O—, —OCH2—, —OCH(R7)—CH2O—, —S—, —S(O)2—, —S(O)2N(H)—, —S(O)2N(R7)—, —C(O)NH— or —C(O)N(R7)—. In a further embodiment Y is —O—, —S(O)2—, —S(O)2N(H)— or —S(O)2N(R7)—. In another embodiment Y is —O— or —S(O)2—. In one embodiment R3 is a C1-C7 alkyl group optionally interrupted by —O—, —S—, —S(O)—, or —S(O)2— groups. In another embodiment R3 is a C1-C7 alkyl group. In a further embodiment R3 is a C1-C4 alkyl group examples include but are not limited to methyl, ethyl, cyclopropylmethyl, trifluoroethyl. In another embodiment R3 is a cycloalkylalkyl group with examples including but not limited to cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl. In another embodiment R3 is heterocycloalkylalkyl. In another embodiment R3 is a group Z as defined above wherein Z is a mono- or bi-cyclic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. In the latter embodiment Z comprises mono- or bi-cyclic ring system ring systems that furthermore may be fully saturated, partially saturated or aromatic. Examples of monocyclic ring systems that are fully saturated include but are not limited to 5-6 membered ring systems such as cyclohexyl, cyclopentanyl, piperazinyl, tetrahydrofuranyl and piperidinyl. Examples of monocyclic ring systems that are partially saturated include but are not limited to 5-6 membered ring systems such as cyclohexenyl, cyclopentenyl, dihydrofuranyl and tetrahydropyridinyl. piperidinyl. Examples of monocyclic ring systems that are aromatic include but are not limited to 5-6 membered ring systems such as phenyl, pyridyl, pyrimidyl, pyrrazolyl, thiophene-yl, furanyl, oxadiazolyl, thiadizolyl, triazolyl, oxazolyl and thiazolyl. Examples of bicyclic ring systems that are fully saturated include but are not limited to 9-10 membered bicyclic ring systems such as decalinyl, decahydroquinolinyl and decahydroisoquinolinyl. Examples of bicyclic ring systems that are partially saturated include but are not limited to 9-10 membered bicyclic ring systems such as tetrahydronapthyl, tetrahydroquinolinyl and tetrahydroisoquinolinyl. Examples of bicyclic ring systems that are aromatic include but are not limited to 9-10 membered bicyclic ring systems such as napthyl, indolyl, indazolyl, benzimidazolyl, benzthiadiazolyl and imidazopyridinyl. In one further embodiment the mono- or bi-cyclic ring system ring system comprises up to 2 nitrogen atoms and up to 1 sulfur or oxygen atoms. In one embodiment R4 is a C1-C7 alkyl group optionally interrupted by —O—, —S—, —S(O)—, or —S(O)2— groups. In another embodiment R4 is a C1-C7 alkyl group. In a further embodiment R4 is a C1-C4 alkyl group examples include but are not limited to methyl, ethyl, cyclopropylmethyl, trifluoroethyl. In another embodiment R4 is a cycloalkylalkyl group with examples including but not limited to cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl. In another embodiment R4 is heterocycloalkylalkyl. In another embodiment R4 is a group Z as defined above wherein Z is a mono- or bi-cyclic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. In the latter embodiment Z comprises mono- or bi-cyclic ring system ring systems that furthermore may be fully saturated, partially saturated or aromatic. Examples of monocyclic ring systems that are fully saturated include but are not limited to 5-6 membered ring systems such as cyclohexyl, cyclopentanyl, piperazinyl, tetrahydrofuranyl and piperidinyl. Examples of monocyclic ring systems that are partially saturated include but are not limited to 5-6 membered ring systems such as cyclohexenyl, cyclopentenyl, dihydrofuranyl and tetrahydropyridinyl. piperidinyl. Examples of monocyclic ring systems that are aromatic include but are not limited to 5-6 membered ring systems such as phenyl, pyridyl, pyrimidyl, pyrrazolyl, thiophene-yl, furanyl, oxadiazolyl, thiadizolyl, triazolyl, oxazolyl and thiazolyl. Examples of bicyclic ring systems that are fully saturated include but are not limited to 9-10 membered bicyclic ring systems such as decalinyl, decahydroquinolinyl and decahydroisoquinolinyl. Examples of bicyclic ring systems that are partially saturated include but are not limited to 9-10 membered bicyclic ring systems such as tetrahydronapthyl, tetrahydroquinolinyl and tetrahydroisoquinolinyl. Examples of bicyclic ring systems that are aromatic include but are not limited to 9-10 membered bicyclic ring systems such as napthyl, indolyl, indazolyl, benzimidazolyl, benzthiadiazolyl and imidazopyridinyl. In one further embodiment the mono- or bi-cyclic ring system ring system comprises up to 2 nitrogen atoms and up to 1 sulfur or oxygen atoms. Other embodiments include compounds of Formulas III, IV, V, and VI and pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4, R5, X, Y and Z are as defined above. Other embodiments include compounds of Formulas VII, VIII, IX, and X and pharmaceutically acceptable salts thereof wherein R1, R2, R3, R4 R5, X, Y and Z are as defined above. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R2, R3, R4, R5, X, Y and Z are as defined above and R1 is hydrogen. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R3, R4, R5 and Z are as defined above; R1 is hydrogen and R2 is C1-C4 alkyl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O—, —OCH2—, —C(O)—, —S—, —S(O)2—, —S(O)2N(R7)— and —N(R7)S(O)2—. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O—, —S(O)2— and —S(O)2N(R7). Another embodiment comprises compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O— and S(O)2N(R7). A further embodiment comprises compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4, R5, and Z are as defined above and X and Y are independently chosen from a bond and —O—. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from a C1-C7 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, and —S(O)2— groups, cycloalkylalkyl and heterocycloalkylalkyl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from C1-C4 alkyl and cyclopropylmethyl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R5, Z are as defined above and X, Y and are independently chosen from a bond, —S—, —SO2- and —O— and R3 and R4 and are independently chosen from C1-C4 alkyl and cyclopropylmethyl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from a group Z wherein Z is as defined above. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 and R5, X and Y are as defined above and Z is a phenyl ring bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 and R5, X and Y are as defined above, and Z is a mono- or bi-cyclic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 X, Y and Z are as defined above and R5 is NO2, NH2, F, Cl, Br, CN, OH, C1-C4 alkoxy, SR6, S(O)2R6 or S(O)2N(R7)2. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 X, Y and Z are as defined above and R5 is aryl or heteroaryl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R3, R4 X, Y and Z are as defined above and R5 is chlorine or fluorine. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R2, R3, R4, R5, X, Y and Z are as defined above and R1 is hydrogen. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R3, R4, R5 and Z are as defined above; R1 is hydrogen and R2 is C1-C4 alkyl. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O—, —OCH2—, —C(O)—, —S—, —S(O)2—, —S(O)2N(R7)— and —N(R7)S(O)2—. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O—, —S(O)2— and —S(O)2N(R7). Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond, —O— and S(O)2N(R7). Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, and Z are as defined above and X and Y are independently chosen from a bond and —O—. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from a C1-C7 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, and —S(O)2— groups, cycloalkylalkyl and heterocycloalkylalkyl. Other embodiments include compounds of Formulas III, IV, V, and VI wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from C1-C4 alkyl and cyclopropylmethyl. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R5, Z are as defined above and X, Y and are independently chosen from a bond, —S—, —SO2— and —O— and R3 and R4 and are independently chosen from C1-C4 alkyl and cyclopropylmethyl. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R5, X, Y and Z are as defined above and R3 and R4 and are independently chosen from a group Z wherein Z is as defined above. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, X and Y are as defined above and Z is a phenyl ring bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R3, R4 and R5, X and Y are as defined above, and Z is a mono- or bi-cyclic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing ring bearing up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6, COR6. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R4 X, Y and Z are as defined above and R5 is NO2, NH2, F, Cl, Br, CN, OH, C1-C4 alkoxy, SR6, S(O)2R6 or S(O)2N(R7)2. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R4 X, Y and Z are as defined above and R5 is aryl or heteroaryl. Other embodiments include compounds of Formulas VII, VIII, IX, and X wherein R1, R2, R4 X, Y and Z are as defined above and R5 is chlorine or fluorine. The compounds of formulas I-IX are expected to alter the activity of γ-secretase and are expected to be useful for the treatment of Alzheimer's disease and other neurodegenerative disorders. In another embodiment A is CO2H. In another embodiment a compound of formula (I) is selected. In another embodiment a compound of formula (II) is selected. In another embodiment a compound of formula (III) is selected. In another embodiment a compound of formula (IV) is selected. In another embodiment a compound of formula (V) is selected. In another embodiment a compound of formula (VI) is selected. In another embodiment a compound of formula (VII) is selected. In another embodiment a compound of formula (VIII) is selected. In another embodiment a compound of formula (IX) is selected. In another embodiment R1 and R2 are independently selected from: H, (C1-C6)alkyl, (C0-C3)alkyl-(C3-C7)cycloalkyl, C1-C6 alkyl that is independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups or heterocycloalkylalkyl wherein each alkyl or cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, cyano, oxo, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously or
In another embodiment R1 and R2 are independently selected from: H, (C1-C6)alkyl, (C0-C3)alkyl-(C3-C7)cycloalkyl wherein each alkyl or cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 are independently selected from: H, (C1-C6)alkyl, wherein alkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 are independently selected from: H, (C3-C6)alkyl, wherein alkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 are independently selected from: H, n-propyl, iso-propyl, iso-butyl, n-butyl, iso-pentyl, and n-pentyl wherein alkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 is H. In another embodiment R1 is H and R2 is n-propyl. In another embodiment R1 is H and R2 is iso-butyl. In another embodiment R1 is H and R2 is n-butyl. In another embodiment R1 is H and R2 is iso-pentyl. In another embodiment R1 is H and R2 is n-pentyl. In another embodiment R1 and R2 are independently selected from: H, (C0-C3)alkyl-(C3-C7)cycloalkyl wherein cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 are independently selected from: H, (C0-C1)alkyl-(C3-C7)cycloalkyl wherein cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 are independently selected from: H, (C0-C1)alkyl-(C3-C5)cycloalkyl wherein cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl provided that R1 and R2 are not H simultaneously. In another embodiment R1 is H and R2 is selected from cyclopentyl, cyclopropylmethyl and cyclobutylmethyl. In another embodiment R1 is H and R2 is cyclopentyl. In another embodiment R1 is H and R2 is cyclopropylmethyl. In another embodiment R1 is H and R2 is cyclobutylmethyl. In another embodiment R1 and R2 are taken together to form a 3-7 membered cycloalkyl or heterocycloalkyl ring which are; optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl or
In another embodiment R1 and R2 are taken together to form a 3-7 membered cycloalkyl or heterocycloalkyl ring which are; optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl. In another embodiment R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring which are; optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl. In another embodiment R1 and R2 are taken together to form a cyclopropyl ring. In another embodiment R1 and R2 are taken together to form a cyclobutyl ring. In another embodiment R1 and R2 are taken together to form a cyclopentyl ring. In another embodiment R1 and R2 are taken together to form a cyclohexyl ring. In another embodiment R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring substituted with R20 and R21 where R20 and R21 are taken together to form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl. In another embodiment R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring substituted on the same carbon atom with R20 and R21 where R20 and R21 are taken together to form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl. In another embodiment R1 and R2 are taken together to form a spiro[2.3]hexane, a spiro[3.3]heptane or a spiro[3.4]octane ring system. In another embodiment R1 and R2 are taken together to form a spiro[2.3]hexane ring system. In another embodiment R1 and R2 are taken together to form a spiro[3.3]heptane ring system. In another embodiment R1 and R2 are taken together to form a spiro[3.4]octane ring system. In another embodiment R1 and R2 are taken together to form a 5,5-disubstituted spiro[2.3]hexane ring system. In another embodiment R1 and R2 are taken together to form a 2,2-disubstituted spiro[3.3]heptane ring system. In another embodiment R1 and R2 are taken together to form a 2,2-disubstituted spiro[3.4]octane ring system. In another embodiment R1 and R2 are independently selected from: H, F, OH, OR6, SR6, NHR7, N(R7)2 NHC(O)R6 or NHCO2R6 provided that R1 and R2 are not H simultaneously. In another embodiment R1 and R2 if not H are unsubstituted, except that when R1 and R2 are taken with the carbon to which they are attached form C3-C7 ring, the ring may be substituted with R20 and R21, which themselves are unsubstituted.
In another embodiment R6 is C1-C6 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (C3-C7)cycloalkyl, (C4-C8) cycloalkylalkyl, heterocycloalkylalkyl. In another embodiment R6 is C1-C6 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups. In another embodiment R6 (C3-C7)cycloalkyl. In another embodiment R6 is a (C0-C3)alkyl-(C3-C7)cycloalkyl In another embodiment R6 heterocycloalkylalkyl. In another embodiment R6 is (CH2)nQ. In another embodiment R6 is —CH2-Q. In another embodiment Q is aryl. In another embodiment Q is heteroaryl. In another embodiment Q is monocyclic heteroaryl. In another embodiment Q is bicyclic heteroaryl. In another embodiment X is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S— or —CH2SCH2—. In another embodiment X is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2O—, —CH2OCH2—, or —CH2CH2O. In another embodiment X is a bond or a divalent linking group selected from —CH2—, —C(O)—, —CH═CH— or —CH2CH2— In another embodiment X is a bond or a divalent linking group selected from —S—, —SCH2—, CH2S— or —CH2SCH2—. In another embodiment X is a bond or a divalent linking group selected from —O— or —S—. In another embodiment X is a bond. In another embodiment X is the divalent linking group —O—. In another embodiment X is the divalent linking group —S—. In another embodiment Y is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S— or —CH2SCH2—. In another embodiment Y is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2O—, —CH2OCH2—, or —CH2CH2O In another embodiment Y is a bond or a divalent linking group selected from —CH2—, —C(O)—, —CH═CH— or —CH2CH2—. In another embodiment Y is a bond or a divalent linking group selected from —S—, —SCH2—, CH2S— or —CH2SCH2—. In another embodiment Y is a bond or a divalent linking group selected from —O— or —S—. In another embodiment Y is a bond. In another embodiment Y is the divalent linking group —O—. In another embodiment Y is the divalent linking group —S—. In another embodiment R3 is a C1-C4 alkyl group. In another embodiment R3 is a C1-C3 alkyl group. In another embodiment R3 is a C2-C3 alkyl group. In another embodiment R3 is selected from ethyl, n-propyl, iso-propyl, trifluoroethyl, or trifluoropropyl. In another embodiment R3 is ethyl. In another embodiment R3 is n-propyl. In another embodiment R3 is iso-propyl. In another embodiment R3 is trifluoroethyl. In another embodiment R3 is trifluoropropyl. In another embodiment R3 is a (C4-C10) cycloalkylalkyl group. In another embodiment R3 is a (C0-C3)alkyl-(C3-C7) cycloalkyl group. In another embodiment R3 is a (C3-C7) cycloalkyl group. In another embodiment R3 is a (C1-C3)alkyl-(C3-C7) cycloalkyl group. In another embodiment R3 is a (C1)alkyl-(C3-C7) cycloalkyl group. In another embodiment R3 is a (C1)alkyl-(C3-C4) cycloalkyl group. In another embodiment R3 is a cyclopropylmethyl group. In another embodiment R3 is a cyclobutylmethyl group. In another embodiment R3 is heterocycloalkylalkyl group. In another embodiment R3 is represented by the group Z. In another embodiment R3 is not cyclopropylmethyl In another embodiment Z is monocyclic. In another embodiment Z is bicyclic In another embodiment Z is heteroaryl In another embodiment Z is unsubstituted heteroaryl In another embodiment Z is benzo[b]thiophenyl, benzo[c][1,2,5]oxadiazoyl, benzo[c][1,2,5]thiadiazolyl or benzo[d]thiazolyl In another embodiment Z is benzo[b]thiophenyl or benzo[d]thiazolyl In another embodiment Z is benzo[c][1,2,5]oxadiazoyl or benzo[c][1,2,5]thiadiazolyl In another embodiment Z is benzo[b]thiophenyl In another embodiment Z is benzo[c][1,2,5]oxadiazoyl In another embodiment Z is benzo[c][1,2,5]thiadiazolyl In another embodiment Z is benzo[d]thiazolyl In another embodiment Z is aryl In another embodiment Z is substituted phenyl In another embodiment Z is 4-substituted phenyl In another embodiment Z is optionally substituted with up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, OH, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6 or COR6 In another embodiment Z is optionally substituted with up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, C1-C4 alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, SR6, NHR7, N(R7)2CO2H, CO2R6 or COR6 In another embodiment Z is optionally substituted with up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, C1-C4 alkoxy, aryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6 or SR6 In another embodiment Z is optionally substituted with up to 3 substituents independently selected from halogen, R6, CF3, CN, NO2, C1-C4 alkoxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6 or SR6 In another embodiment Z is optionally substituted with up to 3 substituents independently selected from halogen, C1-C6 alkyl, (C0-C3)alkyl-(C3-C7)cycloalkyl, CF3, C1-C4 alkoxy, or SR6 In another embodiment Z is optionally substituted with up to 3 substituents independently selected from F, Cl, C1-C3 alkyl, (C3-C6)cycloalkyl, CF3, C1-C4 alkoxy, S—(C1-C4)alkyl or S—(C0-C3)alkyl-(C3-C7)cycloalkyl In another embodiment Z is optionally substituted with up to 3 substituents independently selected from F, Cl, C1-C3 alkyl, (C3-C6)cycloalkyl, CF3, C1-C4 alkoxy, or S—(C1-C3)alkyl In another embodiment Z is substituted CF3, OCF3, OCH2CF3, F, Cl, SMe, Me, Et, iPr In another embodiment Z is substituted with F In another embodiment Z is substituted with Cl In another embodiment Z is substituted with C1-C3 alkyl In another embodiment Z is substituted with (C3-C6)cycloalkyl In another embodiment Z is substituted with CF3, In another embodiment Z is substituted with C1-C4 alkoxy In another embodiment Z is substituted with S—(C1-C3)alkyl In another embodiment R4 is a C1-C7 alkyl group. In another embodiment R4 is a C1-C4 alkyl group. In another embodiment R4 is a C1-C3 alkyl group. In another embodiment R4 is a C2-C3 alkyl group. In another embodiment R4 is selected from ethyl, n-propyl, iso-propyl, trifluoroethyl, or trifluoropropyl. In another embodiment R4 is ethyl. In another embodiment R4 is n-propyl. In another embodiment R4 is iso-propyl. In another embodiment R4 is trifluoroethyl. In another embodiment R4 is trifluoropropyl. In another embodiment R4 is a (C4-C10) cycloalkylalkyl group. In another embodiment R4 is a (C0-C3)alkyl-(C3-C7) cycloalkyl group. In another embodiment R4 is a (C3-C7) cycloalkyl group. In another embodiment R4 is a (C1-C3)alkyl-(C3-C7) cycloalkyl group. In another embodiment R4 is a (C1)alkyl-(C3-C7) cycloalkyl group. In another embodiment R4 is a (C1)alkyl-(C3-C4) cycloalkyl group. In another embodiment R4 is a cyclopropylmethyl group. In another embodiment R4 is a cyclobutylmethyl group. In another embodiment R4 is heterocycloalkylalkyl group. In another embodiment R4 is represented by the group Z. In another embodiment R4 is not cyclopropylmethyl In another embodiment R5 is, F, Cl, Br, CN, C1-C4 alkoxy, SR6, (C1-C4) alkyl, (C0-C3)alkyl-(C3-C7) cycloalkyl, —(C3-C7) cycloalkly or (C2-C4) alkynyl, where each alkyl or cycloalkly is optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl. In another embodiment R5 is, F, Cl, Br, CN, C1-C4 alkoxy, SR6, (C1-C4) alkyl, (C0-C3)alkyl-(C3-C7) cycloalkyl, —(C3-C7) cycloalkly or (C2-C4) alkynyl, where each alkyl or cycloalkly is optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl. In another embodiment R5 is F, Cl, Br, CN, C1-C4 alkoxy, —S—(C1-C4)alkyl or (C1-C4) alkyl, where each alkyl is optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl. In another embodiment R5 is F, Cl, Br, CN, C1-C3 alkoxy —S—(C1-C3)alkyl or (C1-C3) alkyl, where each alkyl is optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl. In another embodiment R5 is F, Cl, Br or CN. In another embodiment R5 is F or Cl. In another embodiment R5 is F. In another embodiment R5 is Cl. In another embodiment R5 is Br. In another embodiment R5 is CN. In another embodiment R5 is C1-C3 alkoxy —S—(C1-C3)alkyl or (C1-C3) alkyl. In another embodiment R5 is C1-C3 alkoxy. In another embodiment R5 is tri-fluoroethoxy or tri-fluoropropoxy. In another embodiment R5 is (C1-C3) alkyl. In another embodiment R5 is CF3. In another embodiment R5 is —S—(C1-C3)alkyl. In another embodiment R5 is —S-Me, —S-Et or —S—CH2CF3. In another embodiment R5 is SR6. In another embodiment R5 is (C0-C3)alkyl-(C3-C7) cycloalkyl, (C2-C4) alkynyl, or —(C3-C7) cycloalkyl. In another embodiment R5 is (C0-C3)alkyl-(C3-C7) cycloalkyl. In another embodiment R5 is (C2-C4) alkynyl. In another embodiment R5 is trifluoroethynyl. In another embodiment R5 is (C3-C7) cycloalkyl. In another embodiment R5 is cyclopropyl. In another embodiment R5 is NO2 or NH2. In another embodiment R5 is aryl or heteroaryl. In another embodiment the compound is a compound selected from examples 100-3217. In another embodiment a racemic compound described in the disclosure is selected.
In a separate embodiment, a method for treating a neurodegenerative disorder comprising administering to a patient an effective amount of the pharmaceutical composition of the previous embodiments. In another embodiment a method for treating Alzheimer's Disease comprising administering to a patient an effective amount of the pharmaceutical composition of the previous embodiments. In the case compounds of Formula (I-IX) may contain asymmetric centers and exist as different enantiomers or diastereomers. All enantiomers or diastereomeric forms are embodied herein. Compounds in the disclosure, e.g., compounds of Formulas I-IX, may be in the form of pharmaceutically acceptable salts. The phrase “pharmaceutically acceptable” refers to salts prepared from pharmaceutically acceptable non-toxic bases and acids, including inorganic and organic bases and inorganic and organic acids. Salts derived from inorganic bases include lithium, sodium, potassium, magnesium, calcium and zinc. Salts derived from organic bases include ammonia, primary (e.g. Tromethamine), secondary and tertiary amines, and amino acids (e.g. Lysine). Salts derived from inorganic acids include sulfuric, hydrochloric, phosphoric, methanesulphonic, hydrobromic. Salts derived from organic acids include C1-6 alkyl carboxylic acids, di-carboxylic acids and tricarboxylic acids such as acetic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, adipic acid and citric acid, and alkylsulfonic acids such as methanesulphonic, and aryl sulfonic acids such as para-tolouene sulfonic acid and benzene sulfonic acid. For detailed list of slats see P. H. Stahl and C. G. Wermuth (eds.) “Handbook of Pharmaceutical Salts, Properties, Selection and Use” Wiley-VCH (ISBN 3-906390-26-8) Compounds and pharmaceutically acceptable salts thereof may be in the form of a solvates. This occurs when a compound of formula (I-IX)) crystallizes in a manner that it incorporates solvent molecules into the crystal lattice. Examples of solvents forming solvates are water (hydrates), MeOH, EtOH, iPrOH, and acetone. Formulas I-IX cover all solvates of the depicted compounds. Compounds in the disclosure may exist in different crystal forms known as polymorphs. Practitioners of the art will recognize that certain chemical groups may exist in multiple tautomeric forms. The scope of this disclosure is meant to include all such tautomeric forms. For example, a tetrazole may exist in two tautomeric forms, 1-H tetrazole and a 2-H tetrazole. This is depicted in FIGURE below. This example is not meant to be limiting in the scope of tautomeric forms. Practitioners of the art will recognize that certain electrophilic ketones, may exist in a hydrated form. The scope of this disclosure is to include all such hydrated forms. For example, a trifluoromethyl ketone may exist in a hydrated form via addition of water to the carbonyl group. This is depicted in FIGURE below. This example is not meant to be limiting in the scope of hydrated forms. Abbreviations used in the following examples and preparations include:
Described below are compounds within Formulas I and II as well as methods for preparing the compounds and using the compounds to treat one or more symptoms of Alzheimer's disease. The compounds of the disclosure are gamma secretase modulators (GSMs), i.e., compounds that act to shift the relative levels of Aβ peptides produced by γ-secretase. In some cases the compounds alter the relative levels of Aβ peptides produced by γ-secretase without significantly changing the total level of Aβ peptides produced. The tetrasubstituted benzene compounds of Formulas I and II may be prepared by multistep organic synthetic routes from known fluoronitrobenzene and chloronitrobenzene starting materials e.g. 2,4-difluoronitrobenzene, 4-fluoro-2-cyano-nitrobenzene, 3-nitro-4-chlorobenzene, 2,4,5-trifluoronitrobenzene, 2,4,5-trichloronitrobenzene or alternatively from 4-hydroxyphenyl and 4-aminophenyl acetic acid starting materials by one skilled in the art of organic synthesis using established organic synthesis procedures. The 1-position acetic acid moiety common to compounds of Formulas I and II, as the free acid itself or as an ester derivative thereof, is already present in the case of a 4-hydroxyphenyl acetic acid or 4-hydroxyphenyl acetic acid ester starting material. In the case of a 4-fluoronitrobenzene starting materials or intermediates, the acetic acid moiety can be introduced by standard nucleophilic aromatic substitution of the 4-fluoro group with an unsubstituted malonic ester (eg diethyl malonate) or a malonic ester derivative already bearing an R1 group (eg. diethyl 2-isobutylmalonate). Introduction of the X—R3 and Y—R4 groups or intermediate groups that are further elaborated to X—R3 and Y—R4 can be carried out by substitution or manipulation of suitable 3 or 4-position functional groups in appropriate starting materials or intermediates en route to Formulas I and II respectively. In cases where X or Y is a bond, a 3 or 4-position halogen or triflate group is replaced with an aryl or heteroaryl group by carbon-carbon bond forming reaction typically a Suzuki coupling reaction. In cases where X or Y is O, S or N, a 3 or 4-position halogen (eg the corresponding 2-fluoro group of a 2,4-difluoronitrobenzene starting material) substitution reaction is performed using HO—R3 or HS—R3 or H2N—R3 and a base (eg NaH, K2CO3) in a suitable solvent (eg DMF). Compounds where X or Y is —S(O)— or —S(O2)— are prepared by oxidation of compounds where X or Y is S. Compounds where X or Y is —S(O)2N(H)—, —S(O)2N(R5)— can be prepared by conversion of a 3 or 4-position nitro group (eg the nitro group of the nitrobenzene starting material) to a sulfonyl chloride via Sandmeyer reaction followed by addition of the corresponding amine. Compounds where X or Y is N(H)S(O)2— or —N(R5)S(O)2— can be prepared by reduction of a 3 or 4-position nitro group to the corresponding aniline followed by reaction with the corresponding sulfonylchloride. Compounds where X or Y is NHC(O)— or —N(R5)C(O)— can be prepared by reduction of a 3 or 4-position nitro group to the corresponding aniline followed by reaction with the corresponding carboxylic acid chloride. Compounds where X or Y is a —C(O)— can be prepared by addition of an organometallic reagent (e.g., a Grignard reagent or organolithium) to a 3 or 4-position cyano group directly or in a 2-step sequence by addition of an organometallic reagent to a 3 or 4-position carboxaldehyde group followed by oxidation. Compounds where X or Y is —C(O)NH— or C(O)N(R5)—)— can be prepared by addition of a corresponding amine to a 3 or 4-position carboxylic acid which in turn may be prepared by hydrolysis of a 3 or 4-position cyano group. Either aromatic nucleophilic substitution of a 2-fluoro-1-nitrobenzene intermediate or alkylation of a 3 or 4-hydroxybenzene intermediate with the corresponding alkyl bromide or triflate may be used to prepare compounds of Formulas I and II where the R4 group is OCH2CF3, C2-C4 alkoxy, or cyclopropyloxymethyl. Compounds wherein the R4 group is an alkyl, aryl or heteroaryl group attached by a carbon-carbon bond may be prepared by a Suzuki coupling reaction. In this process an aryl or heteroaryl boronic acid or borate ester is reacted with an intermediate compound having a 3 or 4-position halogen or triflate group. This method results in replacement of the halogen or triflate group with an aryl or heteroaryl group which is then bonded to the intermediate at the carbon atom previously bearing the boronic acid or ester group. Compounds wherein the R4 group is a heteroaryl group attached by a carbon-nitrogen bond may be prepared by reacting a 3 or 4-iodo intermediate with a heteroaromatic heterocycle having an acidic N—H group under Ulman reaction or copper catalyzed reaction conditions. Compounds of Formulas I and II wherein A=tetrazole may be prepared from their corresponding nitriles A=CN which are available via dehydration of the corresponding primary amides A=CONH2 whose preparation is described above. Thus, treatment of the nitrile with an azide, such as sodium azide or tributylstanyl azide (Bu3SnN3) at a temperature of 20-100° C., optionally with a solvent such as DMF, THF or DMSO. Compounds of the disclosure of Formula III in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, Y is O, X is a bond, R3 is Z, R4 and R5 are as described previously and thus having general Formula XXIV may be prepared generally as depicted in Scheme 1. Thus, as depicted in Scheme 1 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl or arylalkyl R8 group is introduced in the first step by treating ethyl 4-benzyloxyphenylacetate one equivalent of a suitable deprotonating base such as sodium hydride in an appropriate organic solvent followed by the addition of the corresponding reactive alkyl bromide R8Br such as isobutylbromide to yield XX where R9 is hydrogen. In cases where a second alkyl or aralkyl group is present this alkylation step is repeated using R9Br as an alkylating agent. In cases where a spirocyclic ring is formed by R8 and R9 (e.g. cyclopropyl) then the appropriate dibromide is used (e.g. dibromoethane in the case of cyclopropyl). The benzyl group is then removed under standard catalytic hydrogenation conditions and the resulting phenol is treated with bromine in acetic acid to give the bromophenol intermediate XXI. Nitration of XXI then yields nitrophenol intermediate XXII which then us subjected to a standard base mediated aliphatic or aromatic nucleophilic substitution reaction with an alkyl or aryl halide R4—X to give intermediate XXIII where R4 is alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl, aryl or heteroaryl. This is then followed by introduction of the Z group by standard reactions. Such reactions are exemplified by the well established Suzuki coupling of a substituted aryl or heteroaryl boronic acid derivative Z—B(OH)2 using a suitable palladium(0) catalyst typically bearing with phosphine ligands (e.g. Pd(PPh3)4 or tetrakistriphenylphosphine) in the case where Z is linked by a carbon-carbon bond and by copper (eg CuI) mediated Ulman type coupling of a heteroaryl ring bearing an active N—H group where Z is a heteroaryl ring linked by a nitrogen-carbon bond. After introduction of the Z group, the nitro group is converted to the corresponding aniline by any number of standard reduction conditions (eg SnCl2 reduction). This is followed by conversion of the resulting aniline to the diazonium salt which is then converted “in situ” either directly to R5 either directly in the case where R5 is F, Cl, Br, CN, OH, C1-C4 alkoxy or SR6, by using the appropriate copper salt ie CuCl, CuBr, CuCN or nucleophile ie water, alcohol or thiol or in a subsequent step e.g. oxidation (eg with MCPBA) of the product of thiol coupling when R5 is S(O)2R6; e.g. Suzuki coupling of the bromide product when R5 is heteroaryl e.g. treatment of an intermediate sulfonylchloride obtained via CuCl/SO2 conditions with an amine HN(R7)2, when R5 is S(O)2N(R7)2, e.g. Burton trifluoromethylation reaction of the iodide product (Burton, D. J.; Wiemers, D. M. J. Am. Chem. Soc. 1985, 107, 5014 and 1986, 108, 832; Miller, J. A., Coleman, M. C.; Matthews, R. S. J. Org. Chem. 1993, 58, 2637) when R5 is CF3 Standard ester hydrolysis yields compounds of Formula XXIV. Compounds of the disclosure of Formula III in which R1 is OH, OR6, SR6, NHR7, N(R7)2 NHC(O)R6 or NHCO2R6; R2 is H; Y is O, X is a bond, R3 is Z, R4 and R5 are as described previously and thus having general Formula XXVII may be prepared generally as depicted in Scheme 2. Thus, as depicted in Scheme 2 bromination of intermediates of general Formula XXV, prepared according to Scheme 1, e.g. with N-bromosuccinimide (NBS) yields intermediate XXVI. In a subsequent step the Br atom is replaced by a suitable alkoxide, thiolate or masked amine nucleophile (eg azide or N3). The product of the latter reaction is either directly subjected to ester hydrolysis or further processed in optional steps (eg by conversion the masked amine to an amino group followed by reductive amination to give mono or dialkylamine derivatives, and optionally acylation or carbamoylation of such amine derivatives) and then subjected to final ester hydrolysis to give compounds of Formula XXVII in which R10 is OH, OR6, SR6, NHR7, N(R7)2 NHC(O)R6 or NHCO2R6 Compounds of the disclosure of Formula III and IV in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, X and Y are a bond, R3 and R4 are respectively Z1 and Z2 representing independently chosen Z groups as defined above and R5 is as described previously and thus having general Formula XXX may be prepared generally as depicted in Scheme 3 starting from compounds of general Formula XXII which can be prepared as described in Scheme 1. Compounds of Formula V in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl; X is Q=O, S, or SO2; R5 is F or Cl; R3 and Z are as described previously and thus having general Formula XXXIV may be prepared generally as depicted in Scheme 4. Accordingly, the 4-halo group of 2,4,5-trifluoronitrobenzene or 2,4,5-trichloronitrobenzene is selectively displaced by reaction with a 2-substituted diethylmalonate R8YCH(CO2Et)2 under basic conditions (eg NaH/DMF) followed by hydrolysis and esterification to give intermediate XXXI. Subsequently the 2-halo group undergoes nucleophilic aromatic substitution reaction by treatment with a R3-J-H compound (wherein J is O, S) under basic conditions (eg NaH/DMF) followed by reduction and Sandmeyer reaction to give iodide XXXII. Suzuki coupling then gives intermediates of general formula XXXIII. Introduction of an R9 group may be conducted using alkylation conditions described above. Compounds wherein J is SO2 may be prepared by standard oxidation of intermediates XXXIII wherein J is S. Final products having general Formula XXXIV are then prepared by standard ester hydrolysis. Compounds of Formula IV in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl; X is O; R5 is Cl; R3 and Z are as described previously and thus having general Formula XXXVIII may be prepared generally as depicted in Scheme 5. Accordingly, the 4-fluoro group of 2,4-difluoronitrobenzene is selectively displaced by reaction with a 2-substituted diethylmalonate R8CH2(CO2Et)2 under basic conditions (eg NaH/DMF) followed by hydrolysis and esterification to give intermediate XXXV. Subsequently the 2-halo group undergoes nucleophilic aromatic substitution reaction by treatment with a R3—O—H compound under basic conditions (eg NaH/DMF) followed by reduction and chlorination reaction (eg with N-chlorosuccinimide) to give chloroaniline intermediates of general formula XXXVI. Sandmeyer iodination reaction to followed by Suzuki coupling then gives intermediates of general formula XXXVII. Introduction of an R9 group may be conducted using alkylation conditions described above. Final products having general Formula XXXVIII are then prepared by standard ester hydrolysis. Compounds of Formula IV in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl; X is J=O, S; R5 is NO2, NH2, CN, SR6, SO2R6, SO2N(R7)2 F, Cl, Br; R3 and Z are as described previously and thus having general Formula XLII may be prepared generally as depicted in Scheme 6. Accordingly, the 2-fluoro group of 2,4-difluoronitrobenzene is selectively displaced by reaction with a an alcohol or thiol of formula R3-J-H under basic conditions (eg NaH/DMF). The 4-fluoro group of the resulting product is substituted with diethylmalonate under basic conditions (eg NaH/DMF) followed by hydrolysis and esterification to give intermediates of Formula XXXIX. Reduction of the nitro group of XXXIX followed by nitration of the resulting aniline give nitroaniline intermediates of Formula XL. Sandmeyer iodination reaction, followed by Suzuki coupling and finally alkylation reaction to introduce R8 then gives intermediates of general Formula XLI. The nitro group of XLI may be optionally reduced via any number of standard reduction conditions (eg SnCl2) to an aniline which may in turn optionally be converted to diverse other R5 groups either directly or in multistep procedures. Thus, in the case where R5 is F, Cl, Br, CN, OH, C1-C4 alkoxy or SR6, diazotization of the aniline is followed by direct “in situ” conversion to R5 using the appropriate copper salt ie CuCl, CuBr, CuCN or nucleophile ie water, alcohol or thiol. Intermediates where R5 is S(O)2R6 may be prepared by subsequent step oxidation (eg with MCPBA) of the above products of thiol coupling wherein R5 is SR6. Intermediates where R5 is eg heteroaryl, C2-C4 alkynyl or cyclopropyl may be prepared by subsequent Suzuki coupling of the above products wherein R5 is Br or I. Intermediates where R5 is CF3 may be prepared by Burton reaction of the above products wherein R5 is I. Intermediates where R5 is S(O)2N(R7)2, may be prepared by subsequent reaction of above direct sulfonylchloride products (obtained via CuCl/SO2 conditions) with an amine HN(R7)2, Final products having general Formula XLII are then prepared by optional alkylation reaction to introduce R9 followed by standard ester hydrolysis. ll Compounds of Formula VII in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl; X is J=O, S; R5 is NO2, NH2, CN, SR6, SO2R6, SO2N(R7)2 F, Cl, Br; R3 and Z are as described previously and thus having general Formula XLV may be prepared generally as depicted in Scheme 7. Reduction of the nitro group of XXXIX followed by bromination (eg with NBS) of the resulting aniline and prepared by 1 alkylation reaction to introduce R9 gives bromoaniline intermediates of Formula XLIII Suzuki coupling reaction substitutes Z groups for the Br group to give intermediates of general Formula XLIV. The aniline group in intermediates of Formula XLIV may in turn optionally be converted to diverse other R5 groups either directly or in multistep procedures. Thus, in the case where R5 is F, Cl, Br, CN, OH, C1-C4 alkoxy or SR6, diazotization of the aniline is followed by direct “in situ” conversion to R5 using the appropriate copper salt ie CuCl, CuBr, CuCN or nucleophile ie water, alcohol or thiol. Intermediates where R5 is S(O)2R6 may be prepared by subsequent step oxidation (eg with MCPBA) of the above products of thiol coupling wherein R5 is SR6. Intermediates where R5 is eg heteroaryl, C2-C4 alkynyl or cyclopropyl may be prepared by subsequent Suzuki coupling of the above products wherein R5 is Br or I. Intermediates where R5 is CF3 may be prepared by Burton reaction of the above products wherein R5 is I. Intermediates where R5 is S(O)2N(R7)2, may be prepared by subsequent reaction of above direct sulfonylchloride products (obtained via CuCl/SO2 conditions) with an amine HN(R7)2, Final products having general Formula XLII are then prepared by optional alkylation reaction to introduce R9 followed by standard ester hydrolysis. Compounds of Formula IV in which R1 is R8 an alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl, or an arylalkyl group, R2 is R9 a hydrogen, alkyl, cycloalkylalkyl, heterocycloalkylalkyl, alkoxyalkyl, heteroarylalkyl; X—R3 and R5 are identical (J-R3 in Scheme 8) and are either C1-C4 alkoxy or SR6 groups; and Z is as described previously and thus having general Formula L may be prepared generally as depicted in Scheme 8. Accordingly, the 2 and 6-fluoro groups of 2,4,6-trifluoronitrobenzene are selectively displaced by reaction with a an alcohol or thiol of formula R3-J-H under basic conditions (eg NaH/DMF). The 4-fluoro group of the resulting product is substituted with diethylmalonate under basic conditions (eg NaH/DMF) followed by hydrolysis and esterification to give intermediates of Formula XLVIII. Reduction of the nitro group of followed by Sandmeyer iodination reaction of the resulting aniline gives intermediates of Formula XLVIII. Suzuki coupling and followed by alkylation reaction to introduce R8 then gives intermediates of general Formula XLIX. Final products having general Formula L are then prepared by optional alkylation reaction to introduce R9 followed by standard ester hydrolysis. Compounds of formulas I-IX may be prepared in an enantioselectively, this can be accomplished via resolution via chiral HPLC (CHIRALPAK-AD H (250×4.6 mm, 5 μm). Mobile phase: Hexane (0.1% TFA):IPA (93:7), Flow rate 0.8 mL/min., Diluent Hexane:IPA (90:10); Column temperature 40° C.) or via asymmetric synthesis. The phenyl acetic acids of formula (XXXV) are converted into the corresponding acid chlorides, via treatment with SOCl2 or oxalyl chloride with a catalytic amount of DMF. The reaction is performed in an inert solvent such as CH2Cl2, CHCl3, THF, or toluene at a temperature of 0-80° C. The acid chloride is treated with either (R)- or (S)-4-benzyloxazolidin-2-one to (R isomer depicted-XXXXVI) give the oxazolidinone (XXXVII). The oxazolidinone ( ) is then subjected to a base such as NaHMDs, LiHMDS, KHMDS, BuLi or KOtBu in an inert solvent such as THF, Me-THF or Et2O at a temperature of −78 to 0° C. The subsequent enolate is then treated with the appropriate electrophile to give the alkylated oxazolidinone (XXXVIII). The chiral auxillary is removed under conditions such as LiOH/H2O2 followed by a reductive work up with a reagent such as sodium bi-sulfite to give the desired products of formulas (I-IX). Alternatively the racemic compound of formula (1-IX) may be coupled to the Evans chiral oxazolidinone via an intermediate such as the corresponding acid chloride. Upon completion of the coupling, the reaction produces a mixture of diastereoisomers which may be separated by methods such as flash chromatography or crystallization to give single diastereoisomers or enriched mixtures favouring one diastereoisomer over the other (see scheme 10). The auxillary may be removed as described previously. Examples of enantiomers include but are not limited to;
In a further aspect the compounds of the disclosure are embodied in with distinct examples listed in Tables below. To a stirred solution of ethyl 2-(4-hydroxyphenyl)-4-methylpentanoate E-9 (15 g, 63.55 mmol) in 100 ml of glacial acetic acid at 0° C., slowly added bromine (20.26 g, 64.14 mol) and stirred at same temperature for 2.5 h. After completion the reaction, the reaction mixture was poured into water and neutralized with saturated sodium carbonate solution and extracted with ethyl acetate (300 ml×3). The organic layer was washed with water, saturated sodium bicarbonate solution and brine. The organic layer was then distilled off to yield product ethyl 2-(3-bromo-4-hydroxyphenyl)-4-methylpentanoate. Yield: (16 g, 80%).1H NMR (CDCl3): δ 7.20 (m 2H), 6.80 (d, J=7.9 Hz, 1H), 4.90 (bs, 1H), 4.15 (q, 2H), 3.60 (t, 1H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H). Mass: (315, M+1,100%). Ethyl 2-(3-bromo-4-hydroxyphenyl)-4-methylpentanoate (16 g) was taken in acetic acid (100 ml) and to it added drop wise 70% nitric acid (10 ml) below 15° C. The reaction mixture was stirred for 2 h. After completion of the reaction; it was poured into 300 ml of ice water and extracted with ethyl acetate (300 ml×3). The ethyl acetate layer was washed with bicarbonate solution, water and finally brine solution. The organic layer was then distilled off and the crude residue was purified by column chromatography using Ethyl acetate:hexane (2:3) as eluent provided 12 g of 2-(3-bromo-4-hydroxy-5-nitrophenyl)-4-methylpentanoic acid. The acid was taken in 50 ml of absolute ethanol and 2 ml of concentrated sulfuric acid and refluxed for 1 h. The ethanol layer was distilled off, washed it with water and dried gave 13 g of ethyl 2-(3-bromo-4-hydroxy-5-nitrophenyl)-4-methylpentanoate intermediate.1H NMR (CDCl3): δ 8.20 (s 1H), 7.20 (s, 1H), 4.90 (bs, 1H), 4.15 (q, 2H), 3.60 (t, 1H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H). Mass: (360, M+1,100%). A solution of ethyl 2-(3-bromo-4-hydroxy-5-nitrophenyl)-4-methylpentanoate (4.1 g, 11.26 mmol) was taken in 50 ml of DMSO and to it added Cs2CO3 (3.02 g, 12.39 mmol). The reaction mixture was stirred at room temperature for 15 minutes and then added cyclopropylmethyl bromide (1.67 g, 12.39 mmol) dropwise. After completion of addition, the reaction mixture was stirred at 70° C. for 4 h. After completion of the reaction, it was poured into water (200 ml) and extracted with ethyl acetate (100 ml×3). The ethyl acetate layer was washed with 1N HCl, water and finally brine solution. The organic layer was then distilled off and the crude residue was purified by column chromatography using Ethyl acetate:hexane (1:3) as eluent provided 3 g of ethyl 2-(3-bromo-4-(cyclopropylmethoxy)-5-nitrophenyl)-4-methylpentanoate.1H NMR (CDCl3): δ 8.20 (s 1H), 7.20 (s, 1H), 4.15 (q, 2H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (414, M+1,100%). To a solution of ethyl 2-(3-bromo-4-(cyclopropylmethoxy)-5-nitrophenyl)-4-methylpentanoate (2 g, 4.83 mmol) in 30 ml of DMF/Water (25:5 ml) was added Pd(PPh3)4 (558 mg, 0.483 mmol), Cs2CO3 (5.5 g, 16.9 mmol) and 4-CF3-PhB(OH)2 (1.01 g, 5.31 mmol) and the reaction mixture was stirred at 90° C. for 12 h. After completion of the reaction, it was poured into water (100 ml) and extracted with ethyl acetate (100 ml×3). The ethyl acetate layer was washed with 1N HCl, water and finally brine solution. The organic layer was then distilled off and the crude residue was purified by column chromatography using Ethyl acetate:hexane (2:3) as eluent provided 1.3 g of ethyl 2-(6-(cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate.1H NMR (CDCl3): δ 8.20 (s 1H), 7.40-7.20 (m, 5H), 4.15 (q, 2H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (480, M+1,100%). Ethyl 2-(6-(cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (100 mg, 0.208 mmol) was taken in a mixture of MeOH; THF: Water (30 ml, 10:10:2) and to it added LiOH (30 mg, 0.7 mmol). The reaction mixture was stirred at room temperature for 3 h. After completion of the reaction, it was poured into water (50 ml) and extracted with ethyl acetate (100 ml×2). The ethyl acetate layer was washed with 1N HCl, water and finally brine solution. The organic layer was then distilled off and the crude residue was purified by column chromatography using Ethyl acetate:hexane (1:1) as eluent provided 70 mg of 2-(6-(cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid.1H NMR (CDCl3): δ 8.20 (s 1H), 7.40-7.20 (m, 5H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (452, M+1,100%). Ethyl 2-(6-(cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (300 mg, 0.626 mmo) was taken in 30 ml of Toluene:Water (1:1) and to it added Fe powder (203 mg, 3.62 mmol), Ammonium formate (228 mg, 3.62 mmol). The reaction mixture was refluxed for 3 h and then filtered through celite. The toluene was distilled off under reduced pressure and the crude residue was purified by column chromatography using Ethyl acetate:hexane (2:3) as eluent provided 220 mg of ethyl 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate.1H NMR (CDCl3): δ 7.40-7.20 (m, 5H), 6.90 (s 1H), 4.50 (bs, 2H), 4.15 (q, 2H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (450, M+1,100%). Ethyl 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate. (120 mg, 0.267 mmol) was taken in a mixture of MeOH; THF: Water (30 ml, 10:10:2) and to it added LiOH (30 mg, 0.7 mmol). The reaction mixture was stirred at room temperature for 3 h. After completion of the reaction, it was poured into water (50 ml) and extracted with ethyl acetate (100 ml×2). The ethyl acetate layer was washed with 1N HCl, water and finally brine solution. The organic layer was then distilled off and the crude residue was purified by column chromatography using Ethyl acetate:hexane (1:1) as eluent provided 80 mg of 2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid.1H NMR (CDCl3): δ 7.40-7.20 (m, 5H), 7.00 (s, 1H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (422, M+1,100%). 2-(6-Cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (150 mg, 0.33 mmol) was taken up in 10 ml of 6N HCl and a solution of sodium nitrite (30 mg, 0.40 mmol, 5 ml in water) was added at 0° C. The reaction mixture was stirred for 15 minutes at 0° C. and then poured into a saturated solution of copper (II) chloride in water (25 ml) The reaction mixture was then heated at 70° C. for 3 hours. The mixture was cooled to room temperature and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography using ethyl acetate:hexane (2:3) as eluent to yield 120 mg of ethyl 2-(6-cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate.1H NMR (CDCl3): δ 7.60-7.45 (m, 5H), 7.20 (s 1H), 4.15 (q, 2H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (470, M+1,100%). The ethyl 2-(6-cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate above (120 mg, 0.207 mmol) was taken up in a mixture of MeOH; THF:Water (30 ml, 10:10:2) and LiOH (42 mg, 0.7 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. After completion of the reaction, it was poured into water (50 ml) and extracted with ethyl acetate (2×100 ml). The combined extracts were washed with 1N HCl, water and finally brine solution. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography using ethyl acetate:hexane (1:1) as eluent to yield 105 mg of 2-(6-cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid product.1H NMR (CDCl3): δ 7.65-7.40 (m, 5H), 7.20 (s, 1H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (442, M+1,100%). HPLC Purity (99%). 2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (200 mg, 0.53 mmol) was taken up in 5 ml of 1,2-dichlorobenzene and a solution of BF3-etherate (1.5M, 5 ml) was added at 0° C. The reaction mixture was stirred for 15 minutes at 0° C. and t-butyl nitrite (1.5M, 3 ml) was added in a dropwise manner. The reaction mixture was then heated at 100° C. for 1 hour. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography using ethyl acetate:hexane (2:3) as eluent to provide 120 mg of ethyl 2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate.1H NMR (CDCl3): δ 7.60-7.35 (m, 5H), 7.20 (s 1H), 4.15 (q, 2H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.20 (t, 3H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (453, M+1,100%). The above ethyl 2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (120 mg, 0.267 mmol) was taken up in MeOH; THF: Water (20 ml, 10:10:2) and LiOH (42 mg, 0.7 mmol) was added. The reaction mixture was stirred at room temperature for 3 h. After completion, the reaction was poured into water (50 ml) and extracted with ethyl acetate (2×100 ml). The combined ethyl acetate layers were washed with 1N HCl, water and finally brine solution. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude residue obtained was purified by column chromatography using ethyl acetate:hexane (1:1) as eluent to yield 85 mg of 2-(6-cyclopropylmethoxy)-5-fluoro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid product.1H NMR (CDCl3): δ 7.55-7.30 (m, 5H), 7.10 (s, 1H), 3.60 (t, 1H), 3.45 (d, 2H), 1.95-2.00 (m, 1H), 1.75-1.80 (m, 1H), 1.45-1.50 (m, 1H), 1.00 (m, 6H), 0.35-0.25 (m, 5H). Mass: (425, M+1,100%). HPLC Purity (97%). 2-Isobutylmalonic acid diethyl ester (40.0 g, 0.185 mol) in DMF (50 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 8.0 g, 0.33 mol) in 200 mL DMF (200 mL) over 20 min. at 0° C. under nitrogen. The mixture was stirred for 0.5 h at room temperature, cooled to 0° C. and 1,2,4-trifluoro-5-nitro-benzene (30.0 g, 169.5 mmol) in DMF (150 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 16 h, poured into ice water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave a brown oil which was purified by column chromatography over silica gel (Heptane-EtOAc, gradient) to give 57.0 g (90%) of 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester as yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.87 (dd, J=12.3, 6.0 Hz, 1H), 7.79 (dd, J=10.1, 6.4 Hz, 1H), 4.30-4.18 (m, 4H), 2.27 (d, J=5.8 Hz, 2H), 1.60-1.50 (m, 1H), 1.26 (t, J=7.1 Hz, 6H), 0.82 (d, J=7.0 Hz, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 168.2, 155.1 (d,1JCF=252.3 Hz), 150.9 (d,1JCF=263.2 Hz), 135.7, 135.1, 120.0 (dd,2JCF=26.0,3JCF=4.0 Hz), 113.0 (d,2JCF=29.0 Hz), 62.3, 43.1, 24.9, 23.8, 13.8. The above 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonic acid diethyl ester (57.0 g, 152.8 mmol) was dissolved in AcOH/H2O/EtOH (400 mL/120 mL/50 mL) and the reaction mixture was heated under reflux for 96 h. After cooling the solvent was evaporated under reduced pressure and water (200 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined extracts were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave a yellow oil which crystallized on standing to yield 27 g of 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid. Chromatography of the residual oil (Heptane-EtOAc gradient) gave an additional 3 g of product (72% combined yield).1H NMR (300 MHz, CDCl3/TMS): δ 9.63 (br s, 1H), 7.82 (dd, J=8.8, 6.0 Hz, 1H), 7.38 (dd, J=11.0, 5.8 Hz, 1H), 4.14-4.08 (m, 1H), 2.05-1.95 (m, 1H), 1.76-1.66 (m, 1H), 1.52-1.43 (m, 1H), 0.95-0.92 (m, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 177.6, 158.2 (d,1JCF=232.5 Hz), 150.9 (d,1JCF=262.5 Hz), 136.0, 134.7, 119.0 (d,2JCF=20.0, Hz), 113.1 (d,2JCF=29.4 Hz), 41.7, 41.3, 26.0, 22.6, 21.9. 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid (29.0 g, 0.11 mol) was dissolved in EtOH (200 mL) and H2SO4 (96%) 10 mL added. The reaction mixture was refluxed for 3 h and the solvent evaporated to an oil which was dissolved in EtOAc. Water (150 mL) added and the reaction mixture was extracted with EtOAc (3×100 mL). Organic phases washed with saturated NaHCO3 (50 mL), water (100 mL) and brine (100 mL) then dried under MgSO4. The evaporation of solvent under reduced pressure gave 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester as yellow oil 32.0 g, (97%), which was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 7.81 (dd, J=8.8, 6.2 Hz, 1H), 7.41 (dd, J=11.1, 5.6 Hz, 1H), 4.23-4.05 (m, 3H), 2.04-1.94 (m, 1H), 1.71-1.62 (m, 1H), 1.51-1.42 (m, 1H), 1.25 (t, J=7.1 Hz, 3H), 0.95-0.92 (m, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 171.6, 155.0 (d,1JCF=246.0 Hz), 151.5 (d,1JCF=261.3 Hz), 145.5, 135.7, 118.8 (dd,2JCF=24.0,3JCF=4.0 Hz), 113.0 (d,2JCF=20.0 Hz), 61.6, 41.8, 26.1, 22.5, 22.0, 14.1. Cyclopropylmethanol (10.0 g, 138.8 mmol) was treated with n-BuLi (2.5M in hexane 7.4 g, 46 mL, 115.6 mmol) at −15° C. under nitrogen, and the reaction mixture was stirred 1 h at 25° C. To the mixture was added 2-(2,5-difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester (29 g, 96 mmol) in Cyclopropylmethanol (30 mL) dropwise at 25° C. and the reaction mixture stirred for an additional 16 h. Water (100 mL) was added and the reaction mixture was extracted with EtOAc (3×100 mL). The combined organic phases washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of the solvent under reduced pressure gave a brown oil which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 29.5 g, (81%) of 2-(5-cyclopropylmethoxy-2-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.60 (d, J=9.0 Hz, 1H), 7.15 (d, J=5.7 Hz, 1H), 4.07 (t, J=7.7 Hz, 1H), 4.00-3.80 (m, 4H), 2.01-1.92 (m, 1H), 1.68-1.60 (m, 1H), 1.52-1.43 (m, 1H), 1.34-1.20 (m, 1H), 1.19-1.00 (m, 1H), 0.94 (d, J=6.3 Hz, 6H), 0.65 (d, J=7.7 Hz, 2H), 0.54 (d, J=7.7 Hz, 2H), 0.39 (d, J=4.4 Hz, 2H), 0.25 (d, J=4.4 Hz, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 172.6, 152.7 (d,1JCF=243.4 Hz), 148.8, 138.1, 133.3 (d,2JCF=15.7 Hz), 115.8, 112.6 (d,2JCF=29.5 Hz), 75.1, 70.0, 42.1, 41.7, 26.1, 22.5, 22.2, 10.0, 9.8, 3.4. 2-(5-cyclopropylmethoxy-2-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (10.0 g, 26.4 mmol) was dissolved in EtOH (200 mL) and hydrogenated at 50 psi, 25° C. for 24 h over 10% Pd—C (1 g). The mixture was filtered and the solvent evaporated to give crude a brown oi, which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 6.7 g, (72%) of 2-(5-cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 6.73 (d, J=6.9 Hz, 1H), 6.40 (d, J=11.0 Hz, 1H), 4.00-3.70 (m, 5H), 1.91-1.81 (m, 1H), 1.65-1.56 (m, 1H), 1.51-1.39 (m, 1H), 1.28-1.18 (m, 1H), 1.12-1.00 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.63-0.57 (m, 2H), 0.53-047 (m, 2H), 0.35-0.28 (m, 2H), 0.25-0.18 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 154.8 (d,1JCF=236.0 Hz), 142.6, 136.6 (d,3JCF=11.5 Hz), 114.1 (d,2JCF=16.8 Hz), 111.6 (d,3JCF=4.8 Hz), 101.6 (d,2JCF=28.2 Hz), 73.8, 69.2, 42.1, 40.8, 25.9, 22.7, 22.2, 10.5, 9.8, 3.2. 2-(5-cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (2.9 g, 8.3 mmol) was dissolved in a mixture of EtOH/H2O/H2SO4 (96%) 50 mL/100 mL/2.5 mL at 0° C. A solution of NaNO2 (0.63 g, 9.1 mmol) in water (20 mL) was added dropwise at 0° C. and the reaction mixture was stirred for 20 min. A solution of KI (4.0 g, 24.1 mmol) in water (20 mL) was added dropwise at 0° C. and the reaction mixture was heated 50-60° C. for 2.5 h. The reaction mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with 10% sodium thiosulfate (30 mL) followed by brine (30 mL) and then dried over MgSO4. and solvent evaporated to give crude brown oil, which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 2.2 g, (57%) of 2-(5-cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.46 (d, J=8.8 Hz, 1H), 6.83 (d, J=6.3 Hz, 1H), 4.01-3.83 (m, 5H), 1.96-1.86 (m, 1H), 1.69-1.58 (m, 1H), 1.51-1.39 (m, 1H), 1.28-1.18 (m, 1H), 1.12-1.00 (m, 1H), 0.91 (d, J=6.3 Hz, 6H), 0.66-0.60 (m, 2H), 0.55-047 (m, 2H), 0.42-0.34 (m, 2H), 0.26-0.18 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 173.2, 154.3 (d,1JCF=243.4 Hz), 154.1, 127.1 (d,2JCF=16.2 Hz), 125.5 (d,2JCF=26.4 Hz), 112.3 (d,3JCF=3.6 Hz), 84.6 (d,3JCF=8.4 Hz), 74.5, 69.6, 41.9, 41.5, 26.0, 22.7, 22.2, 10.2, 9.8, 3.3. To a solution of 2-(5-cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.2 g, 0.43 mmol) in anhydrous DME (10 mL) under argon was added 4-trifluoromethylphenylboronic acid (0.1 g, 0.53 mmol), CsF (0.16 g, 1.05 mmol), and Pd(PPh3)4 (0.015 g, 0.013 mmol). The reaction mixture was refluxed for 18 h, a water/EtOAc 15/15 mL mixture was added and the organic phase was separated and dried over MgSO4. The solvent was then evaporated to give a yellow oil which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 0.18 of 2-(2-cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a light yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.70-7.64 (m, 4H), 7.05 (d, J=10.4 Hz, 1H), 7.01 (d, J=6.1 Hz, 1H), 4.09 (t, J=7.7 Hz, 1H), 4.02-3.87 (m, 2H), 3.78 (d, J=6.6 Hz, 2H), 2.04-1.90 (m, 1H), 1.74-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.25-1.05 (m, 2H), 0.95 (d, J=6.3 Hz, 6H), 0.60-0.40 (m, 4H), 0.30-0.10 (m, 4H).13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 154.3 (d,1JCF=239.7 Hz), 151.9, 140.7, 132.0, 129.5, 126.6 (d,2JCF=16.9 Hz), 124.8 (q,3JCF=3.7 Hz), 124.0 (q,1JCF=271.6 Hz), 117.0 (d,2JCF=24.6 Hz), 113.6, 74.1, 69.6, 41.1, 41.5, 26.1, 22.7, 22.2, 10.2, 9.8, 3.2. 2-(2-cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.14 g, 0.29 mmol) was dissolved in a mixture of EtOH/H2O (9 ml/1 ml) and KOH 0.3 g added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were dried over MgSO4 and evaporated under reduced pressure to an oil which was purified by column chromatography over silica gel (Heptane-EtOAc gradient) to give 0.12 g of a white solid. A second chromatography of the solid gave 0.03 g (25%) of pure 2-(2-cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid product as a crystalline white solid. M.P.=110-111° C.,1H NMR (300 MHz, CDCl3/TMS): δ 8.99 (br s 1H), 7.66 (br s, 4H), 7.05 (d, J=9.9 Hz, 1H), 6.94 (d, J=5.2 Hz, 1H), 4.08 (t, J=7.7 Hz, 1H), 3.76 (d, J=6.6 Hz, 2H), 2.04-1.90 (m, 1H), 1.81-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.32-1.05 (m, 2H), 0.94 (d, J=6.0 Hz, 6H), 0.54 (d, J=7.4 Hz, 2H), 0.24 (d, J=3.9 Hz, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.2, 154.7 (d,1JCF=239.8 Hz), 152.0, 140.6, 132.0, 129.9, 129.6, 125.7 (d,2JCF=16.2 Hz), 124.8 (q,3JCF=3.6 Hz), 124.0 (q,1JCF=270 Hz), 117.2 (d,2JCF=25.2 Hz), 113.9, 74.2, 41.3, 29.8, 25.9, 22.8, 22.1, 10.3, 3.2. To a stirred solution of ethyl 2-(4-hydroxyphenyl)acetate (20 g, 0.11 mol) in 200 ml of CCl4, was slowly added bromine (18.8 g, 0.11 mol) dissolved in 10 ml of CCl4 at 0° C. for 30 min. The reaction mass was stirred for another 30 min at 0° C. After completion of the reaction, the mixture was poured onto crushed ice and extracted with DCM (×2). The combined organic layers were washed with water, and 10% sodium bi-sulfite solution, dried over Na2SO4, filtered and concentrated in vacuo to give ethyl 2-(3-bromo-4-hydroxyphenyl)acetate in 78% yield. (22.4 g).1HNMR (CDCl3): 7.42 (s, 1H); 7.14 (d, 1H); 6.97 (d, 1H); 5.53 (bs, 1H); 4.13 (q, 2H); 3.52 (s, 2H); 1.16 (t, 3H). To a stirred solution of ethyl 2-(3-bromo-4-hydroxyphenyl)acetate (20 g, 0.076 molo) in 200 ml of DCM was added MeOH (3.4 ml, 0.84 mol) and the mixture was refluxed. Sulfuryl chloride (6.8 ml 0.846 mol) was slowly added under over a period of 10 min. The reaction mixture was refluxed for a further 5 h. Upon completion of reaction, the mixture was poured onto crushed ice and extracted with DCM (×2). The combined organic layer were washed with 10% NaHCO3 solution and water, dried over Na2SO4, filtered and evaporated under vacuum to give ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate in 60% yield. (13.6 g).1HNMR (CDCl3): 7.37 (s, 1H); 7.27 (s, 1H); 5.68 (bs, 1H); 4.16 (q, 2H); 3.48 (s, 2H); 1.29 (t, 3H). To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (4 g, 0.011 mol) and K2CO3 (2.8 g, 0.02 mol) in 100 ml of DMSO was slowly added cyclopropyl methylbromide (1.46 ml, 0.017 mol) at room temperature. Upon completion of the addition, the reaction mixture was heated at 60° C. for 4 h. Upon completion of the reaction, the mixture was poured onto water and extracted with EtOAc (×2). The combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated in vacuo to give ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate in 72% yield. (93.4 g).1HNMR (CDCl3): 7.38 (bs, 1H); 7.28 (s, 1H); 4.16 (q, 2H); 3.87 (d, 2H); 3.58 (s, 2H); 1.38 (m, 1H); 1.28 (t, 3H); 0.63 (m, 2H); 0.38 (m, 2H). A mixture of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate (4 g, 0.011 mol), 4-Trifluoromethyl phenylboronic acid (2.6 g, 0.012 mol), Palladium Tetrakis (triphenylphosphine) (1.3 g, 0.001 mol), Cesium carbonate (13.1 g, 0.04 mol) in DMF/water mixture (100 ml/5 ml) was stirred overnight at 100° C. Upon completion of reaction, the precipitate were removed by filtration. The filtrate was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by Flash Column Chromatography to give ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate in 57% yield. (2.7 g).1HNMR (CDCl3): 7.69 (bs, 4H); 7.36 (s, 1H); 7.17 (s, 1H); 4.18 (q, 2H); 3.59 (s, 2H); 3.39 (d, 2H); 1.28 (t, 3H); 0.96 (m, 1H); 0.41 (m, 2H); 0.01 (m, 2H). To a suspension of NaH (37 mg, 50% suspension, 0.79 mmol) in 25 ml of DMF was slowly added a mixture of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (300 mg, 0.719 mmol) and cyclopropylmethyl bromide (108 mg, 0.782 mmol) in 20 ml of DMF at 0° C. for 15 min under nitrogen atmosphere. Upon completion of the addition, the mixture was stirred for 15 min at 0° C. The reaction mixture was poured onto crushed ice and extracted with EtOAc (×2). The combined organic layers were washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by Flash column Chromatography to give ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate in 62% yield. (0.210 g).1HNMR (CDCl3): 7.69 (s, 4H); 7.41 (s, 1H); 7.21 (s, 1H); 4.19 (q, 2H); 3.63 (t, 1H); 3.41 (d, 2H); 1.94 (m, 1H); 1.78 (m, 1H); 1.27 (t, 3H); 0.97 (bs, 1H); 0.72 (bs, 1H); 0.42 (m, 4H); 0.13 (m, 2H); 0.1 (m, 2H). A mixture of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (100 mg, 0.214 mmol) and lithium hydroxide monohydrate (27 mg, 0.642 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. Upon completion of reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with EtOAc (×2). The combined organic layers were washed with water, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid in 56% yield. (52.6 mg).1HNMR (CDCl3): 7.71 (s, 4H); 7.42 (s, 1H); 7.23 (s, 1H); 3.68 (t, 1H); 3.41 (d, 2H); 1.93 (m, 1H); 1.77 (m, 1H); 0.97 (bs, 1H); 0.71 (bs, 1H); 0.42 (m, 4H); 0.12 (m, 2H); 0.1 (m, 2H). To a stirred solution compound ethyl 2-(3-bromo-4-hydroxy-5-nitrophenyl)-4-methylpentanoate (6 g), in dry methanol (100 mL) was added Pd(OH)2 under an atmosphere of nitrogen. The reaction mixture was stirred for 5 h under an atmosphere of hydrogen. The reaction mixture was filtered through Celite™, washed with methanol and concentrated to dryness under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(3-amino-5-bromo-4-hydroxyphenyl)-4-methylpentanoate (4 g, 72%).1HNMR (CDCl3, 200 MHz): 6.80 (s, 1H); 6.62 (s, 1H); 5.35 (bs, 1H); 4.13 (q, 2H); 3.41 (t, 1H); 1.93-1.56 (m, 2H); 1.51 (m, 1H); 1.21 (t, 3H), 0.97 (d, 6H). Ethyl 2-(3-amino-5-bromo-4-hydroxyphenyl)-4-methylpentanoate 1 (4 g, 0.012 mol) was dissolved in a mixture of ACN/H2O/HCl 60 mL/30 mL/8 mL at 0° C. A solution of NaNO2 (0.919 g, 1.1 eq) in water (10 mL) was added dropwise at 0° C. and the reaction mixture was stirred for 1 h at 0° C. A solution of CuCl (5.99 g, 0.060 mol) in water (10 mL) was added dropwise to the reaction mixture at 0° C. The reaction mixture was then heated to 50° C. for 2.5 h. upon which the mixture was poured into ice water, extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with water (200 mL) and brine (100 mL), dried over NaSO4 and concentrated in vacuo to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoate as yellow oil 2.2 g, (47.3%).1HNMR (CDCl3, 200 MHz): 7.38 (s, 1H); 7.4 (s, 1H); 5.80 (bs, 1H); 4.13 (q, 2H); 3.51 (t, 1H); 1.93-1.56 (m, 2H); 1.51 (m, 1H); 1.21 (t, 3H), 0.97 (d, 6H); To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoate (2 g, 0.57 mmol) and K2CO3 (1.58 g, 0.011 mol) in dry DMF (20 mL), slowly added trifluoroethyl iodide (7.2 g, 3.39 ml, 0.034 mol) at room temperature. Upon completion of the addition, the reaction mixture was slowly heated to 100° C. for 4 h. Upon completion, the reaction mixture was poured into water and extracted with ethyl acetate (2×50 mL). The combined organic layer were washed with water, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (1.4 g, 60% yield).1HNMR (CDCl3, 400 MHz): 7.43 (s, 1H); 7.34 (s, 1H); 4.4 (q, 2H), 4.13 (q, 2H); 3.55 (t, 1H); 1.93 (m, 1H), 1.58 (m, 1H); 1.45 (m, 1H); 1.24 (t, 3H), 0.92 (d, 6H); A mixture of ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (1 g, 1 eq), 4-Trifluoromethyl phenylboronic acid (2.6 g, 1.4 eq), Pd(PPh3)4 (1.3 g, 0.1 eq) and Cesium Fluoride (13.1 g, 2 eq) in DME (30 ml) was stirred for overnight at 100° C. Upon completion, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water followed by brine, dried over Na2SO4 and concentrated under vacuo. The residue was purified by Flash Column Chromatography to give ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate in 74% yield (1.08 g).1HNMR (CDCl3, 400 MHz): 7.68 (m, 5H), 7.43 (s, 1H); 7.24 (s, 1H); 4.4 (q, 2H), 4.13 (q, 2H); 3.55 (t, 1H); 1.93 (m, 1H), 1.58 (m, 1H); 1.45 (m, 1H); 1.24 (t, 3H), 0.92 (d, 6H); A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (800 mg, mmol) and lithium hydroxide monohydrate (27 mg, 0.642 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. Upon completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid in 88% yield (670 mg). Or alternatively example 414 may be synthesized via the following procedures: Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.75 g, 1.70 mmol) was dissolved in anhydrous DMF (20 mL), NaH (60% wt. in paraffin oil, 0.049 g, 2.04 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature, upon which isobutyl bromide (0.2 mL, 1.87 mmol), was added in a drop wise manner at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and then saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic layers were washed with water (2×10 mL) and brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a colorless oil, witch was purified by flash column chromatography to give ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.5 g, 59% yield) as a thick liquid. A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.6 g, 1.21 mmol) and lithium hydroxide monohydrate (0.509 g, 12.1 mmol) in MeOH/THF/Water a solvent mixture (10 mL/10 mL/10 mL) was stirred for 4 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×20 mL). The combined organic layers washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methyl pentanoic acid (0.4 g, 72% yield) as a white solid. To a solution of diethyl isobutylmalonate (50.0 g, 231 mmol) in anhydrous DMF (200 mL) cooled in an ice bath was added NaH (60%, 11.1 g, 277 mmol) in small portions. After the addition, the reaction mixture was stirred at 0° C. for 10 min and then at room temperature for 30 min. 5-Chloro-2-nitrobenzotrifluoride (47.3 g, 210 mmol) in anhydrous DMF (50 mL) was added dropwise and the mixture was stirred at room temperature for two days. The DMF was removed under high vacuum and the residue was diluted with ethyl acetate (400 mL). Water (400 mL) was added dropwise; ammonium chloride (25 g) was added and the layers were separated. The organic layer was washed with brine (400 mL), dried over sodium sulfate, and concentrated under reduced pressure to give a red-brown oil, which was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (12:1) to give the desired product diethyl 2-isobutyl-2-(4-nitro-3-(trifluoromethyl)phenyl)malonate (74.4 g, 87%) as a yellow oil:1H NMR (300 MHz, CDCl3): δ 8.07 (s, 1H), 7.94 (d, 2H, J=8.7 Hz), 7.88 (d, 2H, J=8.7 Hz), 4.25 (m, 4H), 2.33 (d, 2H, J=6.6 Hz), 1.51 (m, 1H), 1.26 (t, 6H, J=7.2 Hz), 0.84 (d, 6H, J=6.6 Hz);13C NMR (75 MHz, CDCl3): δ 169.23, 146.71, 142.86, 132.94, 127.94 (q, J=5 Hz), 124.55, 123.12 (q, J=33 Hz), 121.79 (q, J=272 Hz), 62.19, 61.59, 44.16, 24.66, 23.66, 13.89. To a solution of diethyl 2-isobutyl-2-(4-nitro-3-(trifluoromethyl)phenyl)malonate (74.4 g, 184 mmol) in acetic acid (500 mL) were added water (157 mL) and concentrated H2SO4 (55 mL) carefully. The reaction mixture was refluxed for three days and then concentrated under reduced pressure. The residue was diluted with water (400 mL) and extracted with ethyl acetate (6×100 mL). The combined organic extracts were washed with water (400 mL), dried over sodium sulfate, and concentrated under reduced pressure to give a brown oil. The residue was purified by silica-gel flash chromatography eluting with heptane/EtOAc (5:1 and then 2:1) to give 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid (42.5 g, 76%) as a yellowish oil:1H NMR (300 MHz, CDCl3): δ 11.51 (s, 1H, br), 7.87 (d, 1H, J=8.4 Hz), 7.78 (s, 1H), 7.71 (d, 1H, J=8.4 Hz), 3.84 (t, 1H, J=7.8 Hz), 2.06 (m, 1H), 1.72 (m, 1H), 1.49 (m, 1H), 0.95 (d, 3H, J=6.6. Hz), 0.94 (d, 3H, J=6.3 Hz);13C NMR (75 MHz, CDCl3): δ 178.76, 147.09, 143.94, 132.66, 127.70 (q, J=5 Hz), 125.40, 123.95 (q, J=34 Hz), 121.74 (q, J=271 Hz), 42.16, 25.96, 22.44, 22.09. To a solution of 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid (42.3 g, 139 mmol) in absolute ethanol (300 mL) was added concentrated sulfuric acid (95-98%, 9.0 mL) and the solution was heated at reflux overnight. The reaction mixture was concentrated under reduced pressure; the residue was treated with a solution of sodium carbonate (5%, 300 mL) and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with brine (300 mL), dried over sodium sulfate, and concentrated under reduced pressure. Purification by silica-gel flash chromatography eluting with heptane/EtOAc (10:1) gave 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester (38.4 g, 83%) as a yellowish oil:1H NMR (300 MHz, CDCl3): δ 7.90 (d, 1H, J=8.4 Hz), 7.82 (s, 1H), 7.74 (dd, 1H, J=8.4, 1.5 Hz), 4.18 (m, 2H), 3.83 (t, 1H, J=7.5 Hz), 2.06 (m, 1H), 1.70 (m, 1H), 1.50 (m, 1H), 1.27 (t, 3H, J=7.2 Hz), 0.97 (d, 3H, J=6.6 Hz), 0.96 (d, 3H, J=6.3 Hz);13C NMR (75 MHz, CDCl3): δ 172.24, 146.83, 145.04, 132.40, 127.51 (q, J=5 Hz), 125.28, 123.80 (q, J=32 Hz), 121.78 (q, J=272 Hz), 61.45, 49.45, 42.65, 26.03, 22.41, 22.17, 14.10. A suspension of 4-methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester (38.3 g, 115 mmol), tin (II) chloride (87.2 g, 460 mmol) and water (16.6 g, 920 mmol) in ethanol (500 mL) was heated at reflux for four hours. The reaction mixture was concentrated under reduced pressure; the residue was treated with ethyl acetate (300 mL) and aqueous NaOH solution (1 N, 2.5 L). The aqueous layer was extracted with ethyl acetate (3×600 mL). The combined organic layers were washed with brine (1 L), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (10:1) to give 2-(4-amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (31.1 g, 89%) as a yellow oil:1H NMR (300 MHz, CDCl3): δ 7.35 (d, 1H, J=2.1 Hz), 7.27 (dd, 1H, J=8.4, 2.1 Hz), 6.69 (d, 1H, J=8.4 Hz), 4.10 (m, 4H), 3.54 (t, 1H, J=7.8 Hz), 1.91 (m, 1H), 1.58 (m, 1H), 1.44 (m, 1H), 1.21 (t, 3H, J=6.9 Hz), 0.90 (d, 3H, J=6.6 Hz), 0.89 (d, 3H, J=6.6 Hz);13C NMR (75 MHz, CDCl3): δ 174.14, 143.45, 132.22, 128.58, 125.91 (q, J=4 Hz), 124.80 (q, J=271 Hz), 117.35, 113.60 (q, J=29 Hz), 60.60, 48.54, 42.35, 25.77, 22.46, 22.18, 14.04. To sulfuric acid (95-98%, 20.0 mL) was added 2-(4-amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (6.06 g, 20.0 mmol). The mixture was cooled to 0° C. and water (30.0 mL) was added dropwise. A solution of NaNO2 (1.66 g, 24.0 mmol) in water (12 mL) was added dropwise and the mixture was stirred for additional 20 min. A few crystals of urea were added to decompose any excess NaNO2. A solution of cupric nitrate (466 g, 2.00 mol) in water (880 mL) was added, followed by addition of Cu2O (2.86 g, 20.0 mmol). The mixture was stirred for 5 min and diethyl ether (1 L) was added. The organic extract was washed with brine (500 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (20:1) to give 2-(4-hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (2.20 g, 31%) as a yellow oil: HRMS (DIP-CI-MS): calcd for C15H19NO5F3 (M+H)+: 350.1215, found 350.1240;1H NMR (300 MHz, CDCl3): δ 11.13 (s, 1H), 8.29 (s, 1H), 7.90 (s, 1H), 4.15 (m, 2H), 3.69 (t, 1H, J=7.8 Hz), 2.00 (m, 1H), 1.62 (m, 1H), 1.47 (m, 1H), 1.25 (t, 3H, J=7.2 Hz), 0.94 (d, 3H, J=6.3 Hz), 0.93 (d, 3H, J=6.6 Hz);13C NMR (75 MHz, CDCl3): δ 172.75, 152.45, 134.67 (q, J=5 Hz), 134.29, 131.40, 127.90, 122.35, (q, J=271 Hz), 121.42 (q, J=32 Hz), 61.51, 48.76, 42.76, 26.23, 22.60, 22.42, 14.32. To a solution of 2-(4-hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (2.66 g, 7.62 mmol), cyclopropanemethanol (0.60 g, 8.38 mmol) and triphenylphosphine (2.40 g, 9.14 mmol) in anhydrous THF (32 mL) was added diethyl azodicarboxylate (40 wt % solution in toluene, 3.98 g, 9.14 mmol) dropwise. The reaction mixture was stirred at room temperature for two days and then concentrated under reduced pressure. The residue was triturated with THF/hexane (1:5, 3×15 mL). The combined extracts were concentrated under reduced pressure to give a yellow solid, which was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (60:1 and then 10:1) to give 2-(4-cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (1.89 g, 61%) as a colorless oil:1H NMR (300 MHz, CDCl3): δ 7.92 (s, 1H), 7.73 (s, 1H), 4.06 (m, 2H), 3.79 (d, 2H, J=7.2 Hz), 3.64 (t, 1H, J=7.5 Hz), 1.93 (m, 1H), 1.55 (m, 1H), 1.40 (m, 1H), 1.24 (m, 1H), 1.17 (t, 3H, J=6.9 Hz), 0.86 (m, 6H), 0.56 (d, 2H, J=6.6 Hz), 0.27 (m, 2H);13C NMR (75 MHz, CDCl3): δ 172.49, 149.98, 144.40, 135.55, 130.96 (q, J=5 Hz), 128.29, 126.77, (q, J=31 Hz), 122.37 (q, J=272 Hz), 82.03, 61.37, 48.74, 42.66, 26.04, 22.36, 22.32, 14.14, 10.66, 3.39. A mixture of 2-(4-cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (1.85 g, 4.59 mmol) and Pd/C (1.85 g) in ethanol and 1 N HCl (4.60 mL) was hydrogenated under 36 psi H2 in a Parr apparatus. After 4 h, the reaction mixture was filtered through Celite 521®. The filtrate was concentrated under reduced pressure to give a yellow oil. The residue was treated with an aqueous solution of sodium carbonate (3 g in 100 mL of water) and the resulting solution was extracted with ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to give a brown oil, which was purified by silica-gel flash chromatography eluting with a gradient of heptane/ethyl acetate (from 10:1 to 2:1) to give 2-(3-amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.88 g, 51%) as a light pink oil:1H NMR (300 MHz, CDCl3): δ 6.83 (s, 1H), 6.80 (s, 1H), 4.04 (m, 2H), 3.85 (s, 2H), 3.66 (d, 2H, J=6.9 Hz), 3.45 (t, 1H, J=7.8 Hz), 1.84 (m, 1H), 1.49 (m, 1H), 1.39 (m, 1H), 1.22 (m, 1H), 1.14 (t, 3H, J=7.2 Hz), 0.82 (m, 6H), 0.56 (d, 2H, J=7.5 Hz), 0.27 (d, 2H, J=4.5 Hz);13C NMR (75 MHz, CDCl3): δ 173.61, 142.71, 141.25, 135.51, 123.75 (q, J=30 Hz), 123.52 (q, J=271 Hz), 118.46, 115.52 (q, J=5 Hz), 77.88, 60.70, 49.03, 42.53, 25.86, 22.40, 22.31, 14.07, 10.98, 3.19. To a solution of p-toluenesulfonic acid monohydrate (0.308 g, 1.62 mmol) in acetonitrile (2.3 mL) was added 2-(3-amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.20 g, 0.54 mmol). The resulting suspension of the amine salt was cooled in an ice bath. A solution of sodium nitrite (0.0745 g, 1.08 mmol) in water (0.32 mL) was added dropwise, followed by addition of a solution of KI (1.79 g, 10.8 mmol) in water (2.0 mL). The reaction mixture was stirred in the ice bath for one hour and then at room temperature for one hour. TLC showed that the reaction was completed. Water (20 mL) was added and then an aqueous solution of sodium bicarbonate (1 M) to adjust the pH to 8. Ethyl acetate (20 mL) was added for extraction. The organic layer was washed with aqueous Na2S2O4 solution (10%, 20 mL) and brine (20 mL), dried over Na2SO4, and concentrated under reduced pressure to give a brown oil, which was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (30:1) to give 2-(4-cyclopropylmethoxy-3-iodo-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.15 g, 57%) as a yellowish oil:1H NMR (300 MHz, CDCl3): δ 7.93 (s, 1H), 7.52 (s, 1H), 4.11 (m, 2H), 3.83 (d, 2H, J=7.2 Hz), 3.59 (t, 1H, J=7.5 Hz), 1.95 (m, 1H), 1.50 (m, 3H), 1.22 (t, 3H, J=6.9 Hz), 0.91 (d, 3H, J=6.3 Hz), 0.90 (d, 3H, J=6.3 Hz), 0.64 (m, 2H), 0.43 (m, 2H);13C NMR (75 MHz, CDCl3): δ 172.96, 155.55, 142.66, 136.98, 126.94 (q, J=5 Hz), 124.87 (q, J=30 Hz), 122.64 (q, J=272 Hz), 93.73, 79.79, 61.06, 48.53, 42.65, 26.01, 22.39, 14.16, 10.75, 3.36. A mixture of 2-(4-cyclopropylmethoxy-3-iodo-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (0.14 g, 0.29 mmol), 4-(trifluoromethyl)benzeneboronic acid (0.089 g, 0.47 mmol), Pd(dppf)Cl2 (0.023 g, 0.031 mmol) and a solution of aqueous sodium carbonate (2 M, 0.31 mL, 0.62 mmol) in 1,4-dioxane (4 mL) was degassed and heated at 100° C. for ten days. The reaction mixture was concentrated under reduced pressure; the residue was treated with water (30 mL) and ethyl acetate (30 mL). The organic layer was washed with brine (30 mL), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with heptane/ethyl acetate (100:1) to give a colorless oil (0.11 g), which was further purified by flash chromatography on silica gel 100 CB-reversed phase eluting with MeOH/H2O (5:1 to 20:3) to give 2-(6-cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid ethyl ester (0.05 g, 34%) as a white solid:1H NMR (300 MHz, CDCl3/TMS): δ 7.73 (m, 4H), 7.58 (s, 1H), 7.48 (s, 1H), 4.13 (m, 2H), 3.70 (t, 1H, J=7.5 Hz), 3.27 (d, 2H, J=7.2 Hz), 2.00 (m, 1H), 1.67 (m, 2H), 1.51 (m, 1H), 1.25 (t, 3H, J=7.2 Hz), 0.93 (m, 8H), 0.45 (d, 2H, J=7.5 Hz);13C NMR (75 MHz, CDCl3/TMS): δ 173.35, 153.80, 140.99, 135.48, 135.40, 134.05, 130.05 (q, J=32 Hz), 129.88 (q, J=32 Hz), 129.42, 126.41 (q, J=5 Hz), 125.33 (q, J=4 Hz), 124.06 (q, J=270 Hz), 123.48 (q, J=270 Hz), 79.47, 60.98, 49.21, 42.87, 26.19, 22.46, 14.22, 10.56, 3.13. A mixture of 2-(6-cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid ethyl ester (0.04 g, 0.08 mmol) and aqueous KOH (1.4 M, 0.4 mL) in ethanol (5 mL) was stirred at room temperature for two days. After the solvent was removed under reduced pressure, the residue was diluted with water (30 mL), acidified with 1 N HCl to pH 1, and then extracted with ethyl acetate (30 mL). The organic layer was dried over sodium sulfate, concentrated under reduced pressure and freeze-dried overnight to give the desired carboxylic acid 2-(6-cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid (0.04 g, 100%) as a white solid: mp 148-149° C.; HRMS (ESI-TOF): calcd for C24H23O3F6Na2 (M−H+2 Na)+: 519.1341, found 519.1366;1H NMR (300 MHz, CDCl3/TMS): δ 7.72 (m, 4H), 7.59 (s, 1H), 7.48 (s, 1H), 3.73 (m, 1H), 3.27 (d, 2H, J=6.9 Hz), 2.02 (m, 1H), 1.69 (m, 1H), 1.56 (m, 1H), 1.28 (m, 1H), 0.94 (m, 8H), 0.46 (m, 2H); the proton of COOH was not observed;13C NMR (75 MHz, CDCl3/TMS): δ 178.95, 154.12, 140.82, 135.61, 134.49, 134.24, 130.18 (q, J=32 Hz), 129.44 (q, J=32 Hz), 129.40, 126.50 (q, J=5 Hz), 125.39 (q, J=4 Hz), 124.04 (q, J=270 Hz), 123.40 (q, J=271 Hz), 79.55, 48.91, 42.35, 26.07, 22.49, 22.35, 10.58, 3.15; HPLC purity: 95.2%, retention time=11.78 min. To a solution of 2-(5-cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.2 g, 0.43 mmol) in DME (anhydrous, 10 mL) under argon atmosphere was added 4-trifluoromethylphenylboronic acid (0.1 g, 0.53 mmol), CsF (0.16 g, 1.05 mmol), and Pd(PPh3)4 (0.015 g, 0.013 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatograph using Heptane-EtOAc (60:1-9:1) to give cyclopropylmethyl 2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-5-(cyclopropylmethoxy)-2-fluorophenyl)-4-methylpentanoate as a yellowish oil (0.18 g, 90%).1H NMR (300 MHz, CDCl3/TMS): δ 7.70-7.64 (m, 4H), 7.05 (d, J=10.4 Hz, 1H), 7.01 (d, J=6.1 Hz, 1H), 4.09 (t, J=7.7 Hz, 1H), 4.02-3.87 (m, 2H), 3.78 (d, J=6.6 Hz, 2H), 2.04-1.90 (m, 1H), 1.74-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.25-1.05 (m, 2H), 0.95 (d, J=6.3 Hz, 6H), 0.60-0.40 (m, 4H), 0.30-0.10 (m, 4H).13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 154.3 (d,1JCF=239.7 Hz), 151.9, 140.7, 132.0, 129.5, 126.6 (d,2JCF=16.9 Hz), 124.8 (q,3JCF=3.7 Hz), 124.0 (q,1JCF=271.6 Hz), 117.0 (d,2JCF=24.6 Hz), 113.6, 74.1, 69.6, 41.1, 41.5, 26.1, 22.7, 22.2, 10.2, 9.8, 3.2. Cyclopropylmethyl 2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-5-(cyclopropylmethoxy)-2-fluorophenyl)-4-methylpentanoate (0.14 g, 0.29 mmol) was dissolved in a mixture of EtOH/H2O (9 mL/1 mL) and KOH (0.3 g) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5, and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give a colorless oil. Purification by gradient column chromatography on silica gel Heptane-EtOAc (50:1-9:1) gave 2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-5-(cyclopropylmethoxy)-2-fluorophenyl)-4-methylpentanoic acid as a white solid (0.12 g, quantitative); pure portion (0.03 g, 25%); white microcrystals, M.P.=110-111° C.,1H NMR (300 MHz, CDCl3/TMS): δ 8.99 (br s, 1H), 7.66 (br s, 4H), 7.05 (d, J=9.9 Hz, 1H), 6.94 (d, J=5.2 Hz, 1H), 4.08 (t, J=7.7 Hz, 1H), 3.76 (d, J=6.6 Hz, 2H), 2.04-1.90 (m, 1H), 1.81-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.32-1.05 (m, 2H), 0.94 (d, J=6.0 Hz, 6H), 0.54 (d, J=7.4 Hz, 2H), 0.24 (d, J=3.9 Hz, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.2, 154.7 (d,1JCF=239.8 Hz), 152.0, 140.6, 132.0, 129.9, 129.6, 125.7 (d,2JCF=16.2 Hz), 124.8 (q,3JCF=3.6 Hz), 124.0 (q,1JCF=270 Hz), 117.2 (d,2JCF=25.2 Hz), 113.9, 74.2, 41.3, 29.8, 25.9, 22.8, 22.1, 10.3, 3.2. To a solution of 2-isobutylmalonic acid diethyl ester (75.0 g, 0.35 mol) in DMF (200 mL) was added sodium hydride (60% in mineral oil, 13.0 g, 0.57 mol) over 20 min. at 0° C. The reaction mixture was stirred at 0° C. for 0.5 h, then warmed to 25° C. The reaction mixture was cooled down to 0° C. again and a solution of 2,4-difluoronitro-benzene (50.0 g, 0.31 mol) in DMF (150 mL) was added dropwise at 0° C. The reaction mixture was stirred at 25° C. for 16 h. After cooling, the reaction mixture was poured into ice water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic phases washed with water (3×100 mL), brine (100 mL), and dried (MgSO4). Evaporation of the solvent under reduced pressure gave a brown oil. The crude product (92.0 g, 82%) was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 8.03 (t, J=8.4 Hz, 1H), 7.70 (dd, J=12.9, 1.7 Hz, 1H), 7.47 (d, J=8.5 Hz, 1H), 4.25-4.18 (m, 4H), 2.28 (d, J=6.3 Hz, 2H), 1.54-1.45 (m, 1H), 1.25 (t, J=7.0 Hz, 6H), 0.82 (d, J=7.0 Hz, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 169.2, 154.5 (d,1JCF=263.1 Hz), 146.9 (d, unresolved), 125.3, 124.1 (d,3JCF=3.6 Hz), 118.6 (d,2JCF=23.3 Hz), 62.0, 60.3, 44.1, 24.7, 23.6, 13.9. 2-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid diethyl ester (92.0 g, 0.26 mol) was dissolved in AcOH/H2O/H2SO4 (96%) (500 mL/200 mL/70 mL) and the reaction mixture was refluxed for 24 h. After cooling and evaporation, water (300 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). The evaporation of solvent under reduced pressure gave a brown oil (61 g, quantitative), which was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 8.07-8.01 (m, 1H), 7.33-7.26 (m, 2H), 3.79-3.73 (m, 1H), 2.05-1.95 (m, 1H), 1.76-1.66 (m, 1H), 1.52-1.43 (m, 1H), 0.95-0.92 (m, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 178.3, 156.0 (d,1JCF=232.5 Hz), 147.0, 136.0, 126.2, 124.3, 118.1 (d,2JCF=30 Hz), 49.3, 42.0, 25.8, 22.4, 22.0. 2-(3-Fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid (29.0 g, 0.12 mmol) was dissolved in EtOH (100 mL) and H2SO4 (96%, 5 mL) was added. The reaction mixture was refluxed for 3 h and the solvent evaporated. Water (100 mL) was added and the reaction mixture was extracted with EtOAc (3×100 mL). The combined organic phases were washed with saturated NaHCO3 solution (50 mL), water (100 mL) and brine (100 mL), and then dried over MgSO4. Evaporation of the solvent under reduced pressure gave a brown oil (31.0 g, 97%), which was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 8.03 (t, J=8.4 Hz, 1H), 7.33-7.26 (m, 2H), 4.17-4.11 (m, 2H), 3.73 (t, J=7.6 Hz, 1H), 2.10-1.94 (m, 1H), 1.71-1.62 (m, 1H), 1.51-1.42 (m, 1H), 1.25 (t, J=7.0 Hz, 3H), 0.95-0.92 (m, 6H);13C NMR (75 MHz, CDCl3/TMS): δ 172.2, 155.3 (d,1JCF=265.0 Hz), 148.3 (d,3JCF=8.4 Hz), 136.5, 126.1, 124.1 (d,3JCF=3.6 Hz), 117.8 (d,2JCF=21.6 Hz), 61.3, 49.4, 42.3, 25.9, 22.5, 22.1, 14.1. Cyclopropylmethanol (80.0 g, 1.11 mol) was treated with n-BuLi (2.5 M in hexane, 9.1 g, 57 mL, 0.14 mol) at a temperature ranging from −15 to 0° C. The reaction mixture was stirred for 1 h at 25° C. Then, a solution of 2-(3-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester in cyclopropylmethanol (30 mL) was added at 25° C. and the reaction mixture was stirred for 16 h. Water (100 mL) was added and the reaction mixture was extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL), and dried (MgSO4). Evaporation of the solvent under reduced pressure gave a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (9:1-4:1) to give 2-(3-cyclopropylmethoxy-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (34.0 g, 93%).1H NMR (300 MHz, CDCl3/TMS): δ 7.78 (d, J=8.4 Hz, 1H), 7.06 (s, 1H), 6.97 (d, J=8.4 Hz, 1H), 4.00-3.83 (m, 4H), 3.69 (t, J=8.0 Hz, 1H), 2.07-1.92 (m, 1H), 1.69-1.60 (m, 1H), 1.52-1.42 (m, 1H), 1.32-1.20 (m, 1H), 1.19-1.00 (m, 1H), 0.92 (d, J=6.3 Hz, 6H), 0.68-0.62 (m, 2H), 0.56-0.48 (m, 2H), 0.42-0.38 (m, 2H), 0.26-0.21 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 172.9, 152.3, 146.2, 138.8, 125.6, 119.8, 114.4, 74.2, 69.8, 49.8, 42.6, 26.0, 22.5, 22.2, 10.0, 9.7, 3.3. 2-(3-Cyclopropylmethoxy-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (34.0 g, 94.2 mmol) was dissolved in AcOH (300 mL) and water (20 mL). Then, Zn powder (60.0 g, 923 mmol) was added in portions. The reaction mixture was refluxed for 1 h and after cooling the precipitate was filtered. The solvent was evaporated and water (150 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL) and the combined organic phases were washed with water (3×100 mL) and brine (100 mL). Drying of the organic phase was performed with magnesium sulfate. The evaporation of the solvent gave crude product as a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give 2-(4-amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (23 g, 75%).1H NMR (300 MHz, CDCl3/TMS): δ 6.73-6.61 (m, 3H), 3.94-3.78 (m, 6H), 3.53 (t, J=7.7 Hz, 1H), 1.94-1.85 (m, 1H), 1.65-1.56 (m, 1H), 1.52-1.43 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.64-0.58 (m, 2H), 0.53-0.47 (m, 2H), 0.36-0.33 (m, 2H), 0.24-0.21 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 174.6, 146.4, 135.3, 129.3, 120.5, 114.6, 111.2, 73.1, 69.0, 49.2, 42.7, 25.8, 22.6, 22.4, 10.4, 9.8, 3.2. 2-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (16.3 g, 49.1 mmol) was dissolved in chloroform (200 mL) and N-chlorosuccinimide (5.3 g, 0.75 equiv, 39.6 mmol) was added. The reaction mixture was refluxed for 1 h and after cooling treated with 10% potassium carbonate solution (100 mL). The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were dried over magnesium sulfate. Evaporation of the solvent gave the crude product as a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give 2-(4-amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (5 g, 36%).1H NMR (300 MHz, CDCl3/TMS): δ 6.85 (s, 1H), 6.66 (s, 1H), 3.95-3.80 (m, 4H), 3.49 (t, J=7.7 Hz, 1H), 1.94-1.82 (m, 1H), 1.63-1.52 (m, 1H), 1.50-1.40 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.66-0.58 (m, 2H), 0.53-0.47 (m, 2H), 0.37-0.32 (m, 2H), 0.25-0.20 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 146.8, 132.6, 128.7, 120.6, 118.3, 109.4, 73.6, 69.3, 49.0, 42.6, 25.9, 22.6, 22.4, 10.4, 9.8, 3.3. 2-(4-Amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (5.0 g, 13.7 mmol) was dissolved in a mixture of EtOH/H2O/H2SO4 (96%) (65 mL/100 mL/2.5 mL) and the reaction mixture was cooled down to 0° C. A solution of NaNO2 (0.95 g, 13.7 mmol) in water (5 mL) was added dropwise at 0° C. and the reaction mixture was stirred for 30 min. A solution of KI (7.0 g, 42.2 mmol) in water (20 mL) was added dropwise at 0° C. The reaction mixture was heated to 50-60° C. for 2.5 h. The reaction mixture was extracted with EtOAc (3×50 mL). The organic layers were combined and washed with 10% sodium thiosulfate solution (30 mL) followed by brine (30 mL). The organic phase was dried over MgSO4 and the solvent evaporated to give a crude brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give 2-(3-Chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (4.0 g, 62%).1H NMR (300 MHz, CDCl3/TMS): δ 7.07 (s, 1H), 6.66 (s, 1H), 3.95-3.80 (m, 4H), 3.58 (t, J=7.7 Hz, 1H), 1.96-1.89 (m, 1H), 1.66-1.52 (m, 1H), 1.50-1.40 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.91 (d, J=6.6 Hz, 6H), 0.67-0.61 (m, 2H), 0.56-0.50 (m, 2H), 0.45-0.40 (m, 2H), 0.26-0.21 (m, 2H);13C NMR (75 MHz, CDCl3/TMS): δ 173.2, 159.2, 141.6, 139.4, 121.4, 109.8, 90.4, 74.0, 69.7, 49.4, 42.5, 26.0, 22.6, 22.3, 10.2, 9.8, 3.3. To a solution of 2-(3-chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.27 g, 0.57 mmol) in DME (anhydrous, 10 mL) under argon atmosphere were added 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,2,5]oxadiazole (0.15 g, 0.61 mmol), CsF (0.2 g, 1.32 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.021 g, 0.029 mmol, need 0.06 mmol to complete the reaction!). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture water/EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4, then evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography using Heptane-EtOAc (20:1-9:1) to give 2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.11 g, 41%) of as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.83 (d, J=9.3 Hz, 1H), 7.77 (s, 1H), 7.36-7.33 (m, 1H), 7.11 (s, 1H), 6.91 (s, 1H), 4.02-3.81 (m, 4H), 3.67 (t, J=7.7 Hz, 1H), 2.03-1.96 (m, 1H), 1.74-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.20-1.05 (m, 2H), 0.96 (d, J=6.3 Hz, 6H), 0.57-0.47 (m, 4H), 0.28 (br s, 2H), 0.19 (br s, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 173.4, 157.0, 149.2, 148.3, 142.0, 138.7, 135.4, 133.5, 126.4, 121.6, 117.4, 114.9, 110.6, 73.4, 69.8, 49.8, 42.8, 26.1, 22.5, 22.4, 10.0, 9.8, 3.3, 3.1 2-(4-Benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.11 g, 0.23 mmol) was dissolved in a mixture of EtOH/H2O (9 mL/1 mL) and KOH (0.1 g, 1.76 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5, and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give 2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid as a yellow oil (0.068 g, 70%).1H NMR (300 MHz, CDCl3/TMS): δ 8.40 (br s, 1H), 7.70 (d, J=9.3 Hz, 1H), 7.62 (s, 1H), 7.19 (d, J=9.3 Hz, 1H), 6.97 (s, 1H), 6.73 (s, 1H), 3.67 (d, J=6.6 Hz, 2H), 3.52 (t, J=7.7 Hz, 1H), 1.90-1.81 (m, 1H), 1.62-1.53 (m, 1H), 1.50-1.39 (m, 1H), 0.98-0.68 (m, 1H), 0.81 (d, J=6.1 Hz, 6H), 0.37-0.31 (m, 2H), 0.15-0.10 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.1, 157.1, 149.1, 148.3, 141.0, 138.6, 135.3, 133.7, 126.8, 121.6, 117.4, 115.0, 110.9, 73.4, 49.4, 41.9, 25.9, 22.6, 22.3, 10.0, 3.1. To a solution of 2-(3-chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.18 g, 0.38 mmol) in DME (anhydrous, 10 mL) under argon atmosphere were added 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,2,5]thiodiazole (0.15 g, 0.57 mmol), CsF (0.14 g, 0.92 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.02 g, 0.027 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The combined organic phases were dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give 2-(4-benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.08 g, 50%) as a yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.83 (d, J=9.3 Hz, 1H), 7.77 (s, 1H), 7.36-7.33 (m, 1H), 7.11 (s, 1H), 6.91 (s, 1H), 4.02-3.81 (m, 4H), 3.67 (t, J=7.7 Hz, 1H), 2.03-1.96 (m, 1H), 1.74-1.65 (m, 1H), 1.60-1.45 (m, 1H), 1.20-1.05 (m, 2H), 0.96 (d, J=6.3 Hz, 6H), 0.57-0.47 (m, 4H), 0.28 (br s, 2H), 0.19 (br s, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 157.1, 154.7, 154.0, 141.4, 136.8, 133.7, 132.9, 126.9, 122.8, 121.6, 120.0, 110.8, 73.3, 69.7, 49.7, 42.7, 26.1, 22.5, 22.5, 10.0, 9.8, 3.3, 3.1. 2-(4-Benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.08 g, 0.19 mmol) was dissolved in a mixture of EtOH and H2O (9 mL/1 mL) and KOH (0.1 g, 1.76 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5, and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give 2-(4-benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid as a yellow oil (0.038 g, 55%).1H NMR (300 MHz, CDCl3/TMS): δ 8.02 (d, J=9.0 Hz, 1H), 7.96 (s, 1H), 7.53 (d, J=9.0 Hz, 1H), 7.13 (s, 1H), 6.89 (s, 1H), 3.81 (d, J=6.4 Hz, 2H), 3.68 (t, J=7.6 Hz, 1H), 2.04-1.96 (m, 1H), 1.78-1.69 (m, 1H), 1.63-1.55 (m, 1H), 1.10-1.00 (m, 1H), 0.97 (d, J=6.4 Hz, 6H), 0.50-0.39 (m, 2H), 0.22-0.12 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.1, 157.2, 154.6, 154.0, 140.5, 136.7, 134.0, 132.9, 127.8, 122.9, 121.6, 120.1, 111.0, 73.4, 49.4, 42.0, 25.9, 22.6, 22.3, 10.0, 3.1. To a solution of 2-(3-chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.09 g, 0.19 mmol) in DME (anhydrous, 10 mL) under argon atmosphere were added 4-trifluoromethylphenylboronic acid (0.04 g, 0.2 mmol), CsF (0.07 g, 0.46 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.06 g, 0.08 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4, then evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give 2-(2-chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.063 g, 70%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.66 (d, J=8.0 Hz, 2H), 7.43 (d, J=8.0 Hz, 2H), 7.08 (s, 1H), 6.88 (s, 1H), 4.01-3.86 (m, 2H), 3.77 (d, J=6.6 Hz, 2H), 3.65 (t, J=7.9 Hz, 1H), 2.04-1.95 (m, 1H), 1.71-1.62 (m, 1H), 1.59-1.48 (m, 1H), 1.20-1.02 (m, 2H), 0.96-0.94 (m, 6H), 0.56-0.46 (m, 4H), 0.27-0.25 (m, 2H), 0.16-0.15 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 157.0, 141.2, 138.9, 133.6, 130.8 (two signals), 127.8, 124.5 (q), 124.3 (q,1JCF=271.0 Hz), 121.6, 111.0, 73.3, 69.7, 49.6, 42.7, 26.1, 22.6, 22.4, 10.0, 9.8, 3.3, 3.1. 2-(2-Chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.06 g, 0.12 mmol) was dissolved in a mixture of EtOH and H2O (9 mL/1 mL) and KOH (0.1 g, 1.76 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5 and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure to give 2-(2-chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid as a yellowish solid (0.046 g, 85%). M.p.=115-116° C.1H NMR (300 MHz, CDCl3/TMS): δ 7.67 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 7.08 (s, 1H), 6.85 (s, 1H), 3.77 (d, J=6.4 Hz, 2H), 3.65 (t, J=7.7 Hz, 1H), 2.04-1.94 (m, 1H), 1.75-1.66 (m, 1H), 1.60-1.52 (m, 1H), 1.15-0.89 (m, 1H), 0.95 (d, J=6.4 Hz, 6H), 0.54-0.40 (m, 2H), 0.20-0.10 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.0, 157.1, 140.3, 138.8, 133.8, 130.8, 129.3 (q), 128.2, 124.6, 124.3 (q,1JCF=271.0 Hz), 121.6, 111.2, 73.4, 49.4, 42.0, 25.9, 22.6, 22.3, 10.0, 3.0. To a solution of 2-(3-chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.32 g, 0.67 mmol) in DME (anhydrous, 20 mL) under argon atmosphere were added 4-chlorophenylboronic acid (0.13 g, 0.83 mmol), CsF (0.24 g, 1.58 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.05 g, 0.07 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give 2-(2,4′-dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.26 g, 87%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.37 (d, J=8.0 Hz, 2H), 7.24 (d, J=8.2 Hz, 2H), 7.07 (s, 1H), 6.86 (s, 1H), 3.96-3.89 (m, 2H), 3.76 (d, J=6.3 Hz, 2H), 3.63 (t, J=7.7 Hz, 1H), 2.04-1.95 (m, 1H), 1.71-1.48 (m, 2H), 1.21-1.00 (m, 2H), 0.94 (d, J=6.3 Hz, 6H), 0.55-0.48 (m, 4H), 0.27-0.15 (m, 4H).13C NMR (75 MHz, CDCl3/TMS): δ 173.5, 157.1, 140.8, 133.7, 133.5, 133.0, 131.8, 128.1, 127.8, 121.5, 111.1, 73.2, 69.6, 49.6, 42.6, 26.1, 22.6, 22.5, 10.0, 9.8, 3.3, 3.0. 2-(2,4′-Dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.18 g, 0.36 mmol) was dissolved in a mixture of EtOH and H2O (9 mL/1 mL) and KOH (0.2 g, 3.6 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5 and the reaction mixture was extracted with EtOAc (3×10 mL). The organic phase was dried over MgSO4 and evaporated under reduced pressure to give 2-(2,4′-dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid as a yellowish solid (0.15 g, 93%). M.p.=52-53° C.1H NMR (300 MHz, CDCl3/TMS): δ 10.60 (br s, 1H), 7.37 (d, J=8.4 Hz, 1H), 7.22 (d, J=8.4 Hz, 1H), 7.07 (s, 1H), 6.83 (s, 1H), 3.75 (d, J=6.3 Hz, 2H), 3.63 (t, J=7.3 Hz, 1H), 1.99-1.93 (m, 1H), 1.74-1.65 (m, 1H), 1.59-1.51 (m, 1H), 1.11-1.00 (m, 1H), 0.94 (d, J=6.3 Hz, 6H), 0.54-0.40 (m, 2H), 0.22-0.12 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.7, 157.2, 139.7, 134.0, 133.4, 133.1, 131.8, 128.5, 127.9, 121.6, 111.3, 73.3, 49.4, 42.0, 25.9, 22.6, 22.3, 10.0, 3.0. To a solution of 2-(3-chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (0.53 g, 1.11 mmol) in DME (anhydrous, 20 mL) under argon atmosphere were added 4-chlorophenylboronic acid (0.25 g, 1.30 mmol), CsF (0.41 g, 2.70 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (0.24 g, 0.33 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give 4-methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid cyclopropylmethyl ester (0.37 g, 70%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.48-7.42 (m, 2H), 7.17-7.14 (m, 2H), 7.07 (s, 1H), 6.86 (s, 1H), 4.07-3.87 (m, 2H), 3.78 (d, J=6.3 Hz, 2H), 3.64 (t, J=7.7 Hz, 1H), 2.03-1.93 (m, 1H), 1.70-1.49 (m, 2H), 1.21-1.00 (m, 2H), 0.95-0.93 (m, 6H), 0.56-0.49 (m, 4H), 0.27-0.19 (m, 4H).13C NMR (75 MHz, CDCl3/TMS): δ 173.4, 156.9, 141.3, 134.9, 133.6, 132.5, 131.6, 131.2, 129.9, 129.5, 126.6, 121.5, 110.8, 73.2, 69.6, 49.6, 42.6, 26.1, 22.6, 22.4, 10.0, 9.8, 3.3, 3.1. 4-Methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid cyclopropylmethyl ester (0.37 g, 0.75 mmol) was dissolved in a mixture of EtOH and H2O (9 mL/1 mL) and KOH (0.2 g, 3.6 mmol) was added. The reaction mixture was refluxed for 2 h and after cooling the solvent was evaporated. Then, 6 N HCl was added to adjust the pH to 5, and the reaction mixture was extracted with EtOAc (3×10 mL). The organic phase was dried over MgSO4 and evaporated under reduced pressure to give 4-methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid as a white solid (0.30 g, 90%). M.p.=118-119° C.1H NMR (300 MHz, CDCl3/TMS): δ 9.70 (br s, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.42 (d, J=1.6 Hz, 1H), 7.53 (dd, J=8.2, 1.4 Hz, 1H), 7.07 (s, 1H), 6.83 (s, 1H), 3.78 (d, J=6.3 Hz, 2H), 3.63 (t, J=7.3 Hz, 1H), 2.02-1.93 (m, 1H), 1.74-1.65 (m, 1H), 1.59-1.51 (m, 1H), 1.11-1.00 (m, 1H), 0.94 (d, J=6.3 Hz, 6H), 0.54-0.47 (m, 2H), 0.24-0.16 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.4, 157.0, 140.3, 134.8, 133.9, 132.5, 131.6, 131.3, 129.9, 129.6, 127.0, 121.5, 111.1, 73.3, 49.4, 42.0, 25.9, 22.6, 22.3, 10.0, 3.1. To a solution of 2,2,2-trifluoroethanol (28.2 g, 282.0 mmol) in toluene (120 mL) n-BuLi (1.6 M in hexane, 8.0 g, 80 mL, 125.0 mmol) was added at 0° C. and the reaction mixture warmed up to 25° C. A solution of 1,3,5-trifluoronitrobenzene (10.0 g, 56.5 mmol) in toluene (50 mL) was added dropwise. The reaction mixture was refluxed for 30 h and then poured into water (100 mL). The reaction mixture was extracted with EtOAc (3×100 mL). The organic layers were combined and dried over MgSO4. The solvent was evaporated under reduced pressure to give 5-fluoro-2-nitro-1,3-bis-(2,2,2-trifluoro-ethoxy)-benzene as a brown oil (18.0 g, 95%). The product was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 6.47 (d, J=9.4 Hz, 2H), 4.40 (q, J=8.0 Hz, 4H). To a solution of diethyl malonate (18.0 g, 114.9 mmol) in DMF (50 mL) was added sodium hydride (60% in mineral oil, 3.0 g, 125.0 mmol) at 0° C. The reaction mixture was stirred at 25° C. for 0.5 h and a solution of 5-fluoro-2-nitro-1,3-bis-(2,2,2-trifluoro-ethoxy)-benzene (18.0 g, 53.4 mmol) in DMF (30 mL) was added dropwise. The reaction mixture was heated 100° C. for 24 h. After cooling the reaction mixture was poured into water (300 mL) and extracted with EtOAc (3×50 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of the solvent under reduced pressure gave 2-[4-nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-malonic acid diethyl ester as a brown oil (20.8 g, 80%). The crude product was used for the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 6.91 (s, 2H), 4.62 (s, 1H), 4.48 (q, J=8.0 Hz, 4H), 4.28-4.16 (m, 4H), 1.31-1.25 (m, 6H).13C NMR (75 MHz, CDCl3/TMS): δ 166.4, 149.2, 136.7, 132.3, 122.3 (q,1JCF=276.6 Hz), 109.5 (two signals), 67.0 (q,2JCF=36.7 Hz), 61.4, 41.6, 14.0. Crude 2-[4-nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-malonic acid diethyl ester (20.8 g, 43.6 mmol) was dissolved in a mixture of AcOH/12 N HCl (150 mL/150 mL) and the reaction mixture was refluxed for 16 h. The solvent was evaporated and water (100 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL). The organic layers were combined, washed with water (3×100 mL), and dried over MgSO4. The solvent was evaporated under reduced pressure to give a brown solid, which was washed with a mixture of Heptane/Et2O (100 mL/100 mL) to give [4-nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester as a solid (10.0 g, 57%).1H NMR (300 MHz, CDCl3/TMS): δ 6.71 (s, 2H), 4.45 (q, J=7.7 Hz, 4H), 4.18 (q, J=7.2 Hz, 2H), 3.63 (s, 2H), 1.28 (t, J=7.1 Hz, 6H).13C NMR (75 MHz, CDCl3/TMS): δ 169.7, 149.6, 138.5, 132.4, 122.4 (q,1JCF=277.6 Hz), 109.4 (two signals), 67.0 (q,2JCF=37.2 Hz), 61.6, 41.4, 14.2. [4-Nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester (10.0 g, 24.7 mmol) was dissolved in EtOH (200 mL) and hydrogenated at 50 psi, 25° C. for 16 h in the presence of Pd—C catalyst (10%, 1 g). The catalyst was filtered off and the solvent evaporated to give a crude brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give [4-amino-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester as a yellow oil (8.3 g, 90%).1H NMR (300 MHz, CDCl3/TMS): δ 6.52 (s, 2H), 4.37 (q, J=8.0 Hz, 4H), 4.14 (q, J=7.2 Hz, 2H), 3.90 (br s, 2H), 3.48 (s, 2H), 1.25 (t, J=7.2 Hz, 3H).13C NMR (75 MHz, CDCl3/TMS): δ 171.4, 145.0, 126.3, 123.2, (q,1JCF=277.6 Hz), 122.6, 110.0, 109.8 (two signals), 66.8 (q,2JCF=35.5 Hz), 61.0, 41.0, 14.2. [4-Amino-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester (7.1 g, 18.9 mmol) was dissolved in MeCN (50 mL) and p-TsOH×H2O (11.0 g, 57.9 mmol) was added. The reaction mixture was cooled down to −15° C. and NaNO2 (1.6 g, 23.2 mmol) in water (1 mL) was added. The reaction mixture was stirred at −15° C. for 0.5 h; then a solution of KI (15.0 g, 93.8 mmol) in water (10 mL) was added. The reaction mixture was stirred at −15° C. for additional 0.5 h and quenched with 1 N NaHCO3 solution to pH 9-10. After addition of 10% NaHSO3 solution (20 mL), the reaction mixture was extracted with EtOAc (3×50 mL). The combined organic phases were washed with saturated NaCl solution, dried (MgSO4) and evaporated to give crude a brown oil (9.0 g), which was purified by gradient column chromatography on silica gel eluting with Heptane-EtOAc (9:1-3:1) to give [4-iodo-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester as a white solid (3.8 g, 41%).1H NMR (300 MHz, CDCl3/TMS): δ 6.53 (s, 2H), 4.40 (q, J=8.0 Hz, 4H), 4.16 (q, J=7.1 Hz, 2H), 3.56 (s, 2H), 1.26 (t, J=7.2 Hz, 3H).13C NMR (75 MHz, CDCl3/TMS): δ 170.3, 157.7, 136.7, 122.8 (q,1JCF=277.6 Hz), 108.9 (two signals), 78.3, 67.0 (q,2JCF=36.0 Hz), 61.3, 41.2, 14.2. To a solution of [4-iodo-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester (0.8 g, 1.65 mmol) in DME (anhydrous, 15 mL) under argon atmosphere were added 4-trifluoromethylphenylboronic acid (0.4 g, 2.10 mmol), CsF (0.6 g, 3.95 mmol), and Pd(PPh3)4 (0.3 g, 0.26 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give [2,6-bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-acetic acid ethyl ester (0.54 g, 70%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.64 (d, J=8.2 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 6.68 (s, 2H), 4.28-4.16 (6H), 3.63 (s, 2H), 1.29 (t, J=7.2 Hz, 3H).13C NMR (75 MHz, CDCl3/TMS): δ 170.6, 155.3, 136.1, 135.5, 131.0, 129.4, 129.0, 124.4 (q,3JCF=3.9 Hz), 124.2, 122.9, 119.0, 109.2 (two signals), 66.5 (q,2JCF=35.5 Hz), 61.3, 41.5, 14.2. [2,6-Bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-acetic acid ethyl ester (0.52 g, 1.03 mmol) was dissolved in anhydrous DMF (5 mL) and sodium hydride (60% in oil, 0.05 g, 2.08 mmol) was added at 0° C. The reaction mixture was stirred at 0° C. for 20 min and isobutyl bromide (0.15 g, 1.09 mmol) was added. The reaction mixture was stirred for 1 h at the same temperature and at 25° C. for 15 min., followed by addition of saturated ammonium chloride solution (10 mL). The reaction mixture was extracted with ethyl acetate (2×20 mL) and the combined organic phases were washed with water (3×20 mL), saturated sodium chloride solution (10 mL) and dried over magnesium sulfate. Evaporation gave the crude yellow oil (0.56 g), which was purified by silica gel column chromatography with Heptane/EtOAc to give a white solid (0.24 g). The resulting solid was dissolved in EtOH (10 mL), and H2O (1 mL) and potassium hydroxide (0.2 g) were added. The reaction mixture was refluxed for 2 h and solvent evaporated. Then, 6 N HCl was added to adjust the pH to 3-5 and the mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated to give 2-[2,6-Bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-4-methyl-pentanoic acid as a white solid (0.2 g, 40%).1H NMR (300 MHz, CDCl3/TMS): δ 7.65 (d, J=8.1 Hz, 2H), 7.46 (d, J=8.1 Hz, 2H), 6.72 (s, 2H), 4.24 (q, J=8.0 Hz, 4H), 3.69 (t, J=7.7 Hz, 1H), 2.03-1.96 (m, 1H), 1.76-1.67 (m, 1H), 1.60-1.52 (m, 1H), 0.96 (d, J=6.3 Hz, 6H).13C NMR (75 MHz, CDCl3/TMS): δ 179.3, 155.4, 140.6, 135.3, 130.9, 129.6, 129.1, 124.5 (q,3JCF=4 Hz), 124.2 (q,1JCF=272 Hz), 122.9 (q,1JCF=278 Hz), 119.8, 107.9, 66.5 (q,2JCF=36 Hz), 49.7, 42.2, 25.9, 22.6, 22.3. To a solution of 2,4-difluoronitrobenzene (300.0 g, 1.89 mol) and 2,2,2-trifluoroethanol (245.0 g, 2.45 mol) in toluene (600 mL) was added sodium hydroxide (90.5 g, 2.26 mol) in portions over 30 min to keep the temperature between 30 and 40° C. After the temperature had dropped to 30° C., the reaction mixture was heated to 45-50° C. using an oil bath for additional 16 h. After cooling, water (500 mL) and 2.5 N H2SO4 (200-300 mL, for adjustment of pH to 5) were added and the organic layer was separated. The water layer was extracted with EtOAc (2×300 mL). The combined organic layers were washed with saturated sodium chloride solution (100 mL) and dried over magnesium sulfate. The solvent was evaporated to give a yellow oil, which solidified after 30 min to give a yellowish solid (450.0 g, quantitative). The crude product was used in the next step without purification.1H NMR (300 MHz, CDCl3/TMS): δ 8.03-7.98 (m, 1H), 6.93-6.82 (m, 2H), 4.49 (q, J=7.7 Hz, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 165.0 (d,1JCF=259.6 Hz), 152.3 (d,3JCF=13.1 Hz), 128.2 (d,3JCF=11.9 Hz), 122.4 (d,1JCF=273.4 Hz), 110.1 (d,2JCF=22.5 Hz), 105.9 (q,1JCF=242.6 Hz), 104.3 (d,2JCF=26.1 Hz), 67.6 (q,1JCF=36.7 Hz). Acetic acid (1 L) was added to the warm reaction mixture followed by a mixture of concentrated sulfuric acid (325 mL) in water (1 L) in one portion. A precipitate, which was formed initially, dissolved at the end of the addition. Effective stirring was required for this reaction. The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and EtOAc (1000 mL) and water (1000 mL) were added. The organic layer (bottom layer!) was separated. The aqueous solution was extracted with EtOAc (500 mL), the organic phases were combined, washed with water (3×2000 mL), brine (500 mL), and dried over MgSO4 with charcoal. The solvent was evaporated and the solid residue was washed by stirring with heptane/EtOAc (20:1, 500 mL). The solid was filtered and dried in vacuum. The yield of 2-(4-nitro-3-(2,2,2-trifluoro-ethoxy)phenyl)acetic acid was 256 g (65%).1H NMR (300 MHz, CDCl3/TMS): δ 7.80 (d, J=8.3 Hz, 1H), 7.25 (s, 1H), 7.10 (d, J=8.3 Hz, 1H), 5.07 (s, 1H), 4.67 (q, J=8.2 Hz, 2H), 3.70 (s, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 175.0, 151.5, 144.0, 140.3, 126.4, 125.0, 122.2 (d,1JCF=273.0 Hz), 118.0, 67.6 (q,1JCF=36.0 Hz), 42.5. Concentrated sulfuric acid (50 mL) was added slowly to a solution of 2-(4-nitro-3-(2,2,2-trifluoro-ethoxy)phenyl)acetic acid (180 g, 0.64 mol) in MeOH (500 mL). The reaction mixture was stirred at room temperature overnight. The methanol was evaporated and EtOAc (500 mL) was added. The solution was washed with water (2×200 mL) and brine and dried over MgSO4. The solvent was evaporated, the solid residue was stirred with heptane (200 mL), and the solid was filtered. Yield 182.2 g (96%).1H NMR (300 MHz, CDCl3/TMS): δ 7.82 (d, J=8.7 Hz, 1H), 7.07-7.05 (m, 2H), 4.47 (q, J=8.0 Hz, 2H), 3.68 (s, 3H), 3.67 (s, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 170.1, 150.4, 141.2, 139.4, 125.9, 123.9, 122.6 (d,1JCF=277.6 Hz), 117.5, 67.6 (q,1JCF=36.7 Hz), 52.4, 41.0. [4-Nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid methyl ester (33 g, 94.5 mmol) and (bromomethyl)cyclobutane (17 g, 114.1 mmol) were mixed in DMSO (50 mL) and KOH (6.4 g, 114.1 mmol) was added in portions over 15 min. The reaction mixture was stirred for 16 h and water (100 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL). The combined organic phases were dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography using Heptane-EtOAc (9:1-4:1) to give 15 g (40%) of the product as a yellow oil. (The synthesis was repeated with temperature kept at 40° C. over 16 h to give the product in quantitative yield).1H NMR (300 MHz, CDCl3/TMS): δ 7.86 (d, J=8.0 Hz, 1H), 7.12-7.09 (m, 2H), 4.50 (q, J=7.7 Hz, 2H), 3.68 (s, 3H), 3.55 (t, J=7.3 Hz, 1H), 2.22-2.10 (m, 2H), 2.03-1.75 (m, 5H), 1.70-1.55 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 172.9, 150.5, 146.4, 139.4, 126.0, 122.7, 122.6 (d,1JCF=277.6 Hz), 116.0, 67.5 (q,1JCF=36.7 Hz), 52.3, 49.6, 40.7, 33.9, 28.2, 27.9, 18.4. A solution of the 3-cyclobutyl-2-[4-nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-propionic acid methyl ester (15 g, 36.0 mmol) in EtOH (150 mL) was hydrogenated at 50 psi and 25° C. for 16 h in the presence of Pd—C catalyst (10%, 1.5 g). On the next day, the catalyst was filtered off and the solvent evaporated to give the crude product (12.3 g, 88%) as a yellow oil, which was used without purification for the next step.1H NMR (300 MHz, CDCl3/TMS): δ 6.79-6.73 (m, 2H), 6.66 (d, J=8.0 Hz, 1H), 4.36 (q, J=8.3 Hz, 2H), 3.80 (br s, 2H), 3.63 (s, 3H), 3.35 (t, J=7.7 Hz, 1H), 2.20-1.86 (m, 4H), 1.85-1.70 (m, 3H), 1.67-1.51 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 174.7, 146.7, 135.7, 129.1, 123.3 (d,1JCF=277.6 Hz), 122.7, 115.4, 112.2, 66.4 (q,1JCF=35.4 Hz), 51.9, 48.9, 40.8, 34.0, 28.3, 28.1, 18.5. To a solution of the 2-[4-amino-3-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester (12.3 g, 31.8 mmol) in chloroform (150 mL) was added N-bromosuccinimide (7 g, 39.3 mmol). The reaction mixture was stirred at 25° C. for 16 h and a mixture of water and methylene chloride (100 mL/100 mL) was added. The reaction mixture was extracted with methylene chloride (2×50 mL) and the organic phases were separated. The combined organic phases were dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by a short silica gel column chromatography eluting with heptane-EtOAc (4:1) to give the product (13.9 g, 94%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.06 (d, J=1.1 Hz, 1H), 6.70 (d, J=1.2 Hz, 1H), 4.37 (q, J=8.0 Hz, 2H), 4.21 (br s, 2H), 3.64 (s, 3H), 3.31 (t, J=7.7 Hz, 1H), 2.20-1.89 (m, 4H), 1.81-1.75 (m, 3H), 1.67-1.51 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 174.2, 144.6, 134.4, 128.9, 125.7, 123.0 (d,1JCF=277.6 Hz), 110.9, 108.7, 66.5 (q,1JCF=36.0 Hz), 52.0, 48.6, 40.7, 33.9, 28.3, 28.0, 18.5. To a solution of 2-[4-amino-3-bromo-5-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester (13.8 g, 29.6 mmol) in DME (anhydrous, 100 mL) under argon atmosphere were added 4-trifluoromethylphenylboronic acid (6.8 g, 35.8 mmol), CsF (11 g, 72.3 mmol), and Pd(PPh3)4 (3.4 g, 2.94 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). On the next day, a mixture water and EtOAc (100 mL/100 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by a short silica gel column chromatography by use of Heptane-EtOAc (4:1) to give the product (14.7 g, 94%) as a yellowish oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.59 (d, J=8.0 Hz, 2H), 6.78 (dd, J=9.6, 1.4 Hz, 2H), 4.43 (q, J=8.0 Hz, 2H), 3.95 (br s, 2H), 3.66 (s, 3H), 3.39 (t, J=7.7 Hz, 1H), 2.25-2.07 (m, 2H), 2.03-1.91 (m, 2H), 1.88-1.75 (m, 3H), 1.69-1.52 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 174.6, 144.8, 133.1, 129.2, 128.6, 126.3, 125.7 (q,3JCF=3.6 Hz), 123.8, 123.3 (q,1JCF=277.6 Hz), 111.4, 66.5 (q,1JCF=35.4 Hz), 52.0, 49.0, 40.9, 34.1, 28.3, 28.1, 18.5. To a solution of 2-[6-amino-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester (14.7 g, 27.7 mmol) in a mixture of MeCN and H2O (120 mL/120 mL), concentrated HCl (25 mL) was added. The reaction mixture was cooled down to 0-5° C. and a solution of NaNO2 (2.9 g, 42.0 mmol) in water (3 mL) was added dropwise. The reaction mixture was stirred at 0-5° C. for 40 min and CuCl (I) (27 g, 272.7 mmol) was added at once. The reaction mixture was heated at 50° C. for additional 3 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were washed with water (200 mL) and brine (100 mL). The organic phase was dried over MgSO4 and evaporated to give the product (14.5 g, 95%) as a yellow oil.1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 6.98 (dd, J=6.1, 1.6 Hz, 2H), 4.47 (q, J=8.0 Hz, 2H), 3.68 (s, 3H), 3.48 (t, J=7.7 Hz, 1H), 2.20-2.10 (m, 2H), 2.03-1.75 (m, 5H), 1.70-1.52 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 173.6, 153.5, 142.2, 141.0, 138.9, 129.7, 125.0 (q,3JCF=3.6 Hz), 124.8, 124.0 (q,1JCF=271.6 Hz), 126.6 (q,1JCF=278.8 Hz), 121.4, 114.0, 67.3 (q,1JCF=35.4 Hz), 52.2, 49.3, 40.8, 34.0, 28.3, 28.0, 18.5. To a solution of the 2-[6-chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester (8.0 g, 14.5 mmol) in a mixture of the EtOH (100 mL) and H2O (15 mL) was added potassium hydroxide (10 g, 178.5 mmol). The reaction mixture was refluxed for 3 h and the solvent evaporated. Then, 6 N HCl was added to adjust the pH to 3-5 and the mixture was extracted with EtOAc (3×50 mL). The combined organic phases were dried over MgSO4 and evaporated to give 2-[6-chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid as a white solid (7.0 g, 90%).1H NMR (300 MHz, CDCl3/TMS): δ 7.70 (d, J=8.2 Hz, 2H), 7.53 (d, J=8.2 Hz, 2H), 6.98 (s, 2H), 4.47 (q, J=8.0 Hz, 2H), 3.49 (t, J=7.7 Hz, 1H), 2.27-2.13 (m, 2H), 2.06-1.73 (m, 5H), 1.71-1.52 (m, 2H).13C NMR (75 MHz, CDCl3/TMS): δ 179.1, 153.6, 142.1, 141.2, 138.0, 129.7, 125.0 (q,3JCF=3.6 Hz), 124.9, 124.0 (q,1JCF=262.5 Hz), 123.0 (q,1JCF=277.6 Hz), 121.8, 114.3, 67.3 (q,1JCF=36.0 Hz), 49.3, 40.3, 33.9, 28.3, 28.0, 18.5. To a stirred solution of ethyl 2-(4-hydroxyphenyl)acetate (20 g, 0.076 molo) in 200 ml of DCM was added MeOH (3.4 ml, 0.84 mol). The mixture was brought to reflux and sulfuryl chloride (6.8 ml 0.846 mol) dissolved in DCM (50 mL) was slowly added under over 10 min. The reaction mixture was refluxed further for 5 h, upon which the reaction mixture was poured onto crushed ice and extracted with DCM (×2). The combined organic layers were washed with 10% NaHCO3 solution and water. The organic layer was dried over Na2SO4, filtered and evaporated under vacuum to give compound ethyl 2-(3-chloro-4-hydroxyphenyl)acetate in 60% yield. (13.6 g). To a stirred solution of compound ethyl 2-(3-chloro-4-hydroxyphenyl)acetate (11 g, 51 mmol) in 200 ml of CCl4, was slowly added bromine (8.22 g, 51 mmol) as a solution CCl4 (100 ml) at 0° C. over a period of 30 min. The reaction mixture was stirred for a further 30 min at 0° C. Upon which the reaction mixture was poured onto crushed ice and extracted with DCM (2×100 mL). The combined organic layers were washed with water followed by 10% sodium bisulfite solution, dried over Na2SO4 filtered and evaporated under reduced pressure to give ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (12.2 g) as a white solid in 80% yield.1HNMR (CDCl3): 7.37 (s, 1H); 7.27 (s, 1H); 5.68 (bs, 1H); 4.16 (q, 2H); 3.48 (s, 2H); 1.29 (t, 3H). To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (2 g, 6.8 mmol), potassium carbonate (2.35 g, 17.0 mmol) in dry DMF (20 mL), was slowly added trifluoro ethyl iodide (8.58 g, 4.0 mL, 40.8 mmol) at room temperature, the reaction mixture was slowly heated to 100° C. and heating was continued for 4 h. Upon which the reaction mixture was poured onto water and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, dried over Na2SO4 and evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc) to gave compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-acetate (0.750 g, 30% yield).1HNMR (CDCl3, 400 MHz): 7.43 (s, 1H); 7.34 (s, 1H); 4.4 (q, 2H), 4.13 (q, 2H); 3.55 (t, 1H); 1.93 (m, 1H), 1.58 (m, 1H); 1.45 (m, 1H); 1.24 (t, 3H), 0.92 (d, 6H); A mixture of 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-acetate (0.750 g, 2.0 mmol), 4-trifluoromethyl phenylboronic acid (0.567 g, 3.0 mmol), Pd (PPh3)4 (0.231 g, 0.2 mmol), cesium fluoride (0.604 g, 4.0 mmol) in DME (10 ml) was stirred overnight at 100° C., upon which the precipitates were removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water followed by brine and dried over Na2SO4. The crude residue was purified by flash column chromatography to give ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.525 g, 73.6%) as an off white solid. Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (1.0 g, 2.27 mmol) was dissolved in anhydrous DMF (80 mL), NaH (60% wt. in paraffin oil, 0.109 g, 2.72 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature, upon which cyclopropyl methyl bromide (0.24 mL, 2.5 mmol) was added in a dropwise manner at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. upon which saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over Na2SO4, filtered and evaporated under reduced pressure to give colorless oil, which was purified by flash column chromatography to yield compound ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.68 g). A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.68 g, 0.4 mmol) and lithium hydroxide monohydrate (100 mg, 4.6 mmol) in a MeOH/THF/Water solvent mixture (15 ml/15 ml/15/ml) was stirred for 3 h at room temperature. After completion of reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid in 88% yield (0.4 g).1H-NMR (CDCl3, 500 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.43 (s, 1H); 7.24 (s, 1H); 3.98 (q, 2H); 3.72 (t, 1H); 1.94 (m, 1H), 1.78 (m, 1H); 0.71 (m, 1H), 0.46 (m, 2H), 0.02-0.19 (m, 2H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (1.5 g, 3.4 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.163 g, 6.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 1,3-dibromopropane (0.757 g, 3.7 mmol) was added drop wise at 0° C. The reaction mixture was stirred for an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl-1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo butane carboxylate (400 mg). A mixture of ethyl-1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo butane carboxylate (400 mg, 0.83 mmol) and lithium hydroxide monohydrate (0.2 g, 8.3 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. Upon completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by column chromatography to give 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acid in 88% yield (0.21 g).1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.39 (s, 1H); 7.26 (s, 1H); 3.98 (q, 2H); 2.86 (m, 2H); 2.52 (m, 2H); 2.16 (m, 1H), 1.91 (m, 1H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.8 g, 1.81 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.109 g, 4.5 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 1,4-dibromobutane (0.432 g, 1.99 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. upon which saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo pentane carboxylate (400 mg) as a thick liquid. A mixture of compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo pentane carboxylate (100 mg, 0.21 mmol) and lithium hydroxide monohydrate (96 mg, 2.1 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. After completion of reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclopentane carboxylic acid (0.05 g).1H-NMR (CDCl3, 500 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.56 (s, 1H); 7.34 (s, 1H); 3.98 (q, 2H); 2.68 (m, 2H); 1.94 (m, 2H); 1.78 (m, 4H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.4 g, 3.4 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.163 g, 6.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 1-iodo-2-(2-iodoethoxy)ethane (1.2 g, 3.7 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield ethyl 4-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylate (400 mg). A mixture of ethyl 4-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylate (400 mg, 0.78 mmol) and lithium hydroxide monohydrate (0.188 g, 7.8 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. Residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). Combined organic layer was washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 4-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylic acid (100 mg).1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.56 (s, 1H); 7.34 (s, 1H); 3.98 (q, 2H); 3.61 (t, 2H); 2.53 (dd, 2H); 1.99 (m, 2H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 3,3-dimethyl-1,5-dibromopentane (0.322 g, 1.25 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (230 mg). A mixture of compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate (200 mg, 0.37 mmol) and lithium hydroxide monohydrate (88 mg, 3.7 mmol) in a MeOH/THF/Water solvent mixture (5 ml/5 ml5/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylic acid in 67% yield (150 mg).1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.56 (s, 1H); 7.34 (s, 1H); 3.98 (q, 2H); 2.48 (dd, 2H); 1.88 (m, 2H); 1.41 (m, 4H), 0.98 (s, 3H), 0.91 (s, 3H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.5 g, 1.13 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.113 g, 2.8 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 1,5-dibromopentane (0.19 g, 1.24 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexanecarboxylate (0.37 g) as a thick liquid. A mixture of ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexanecarboxylate (0.37 g, 0.72 mmol) and lithium hydroxide monohydrate (0.174 g, 7.28 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexane carboxylic acid (0.25 g) as a white solid.1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.55 (s, 1H); 7.34 (s, 1H); 3.98 (q, 2H); 2.48 (dd, 2H); 1.52-1.81 (m, 6H); 1.33 (m, 2H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.6 g, 1.36 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.136 g, 3.4 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and 1,1-bis(bromomethyl)cyclopropane (0.482 g, 1.4 mmol, for preparation see J. Org. Chem 1993, 58, 4122-26) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 5-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-spiro[2,3]hexane-5-carboxylate (150 mg) as a low melting solid. A mixture of ethyl 5-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-spiro[2,3]hexane-5-carboxylate (0.5 g, 0.9 mmol) and lithium hydroxide monohydrate (0.415 g, 9.88 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. Residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 5-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-spiro[2,3]hexane-5-carboxylic acid (0.29 g).1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.41 (s, 1H); 7.21 (s, 1H); 3.98 (q, 2H); 2.95 (d, 2H); 2.75 (d, 2H), 0.58 (t, 2H), 0.48 (t, 2H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.6 g, 0.49 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.039 g, 1.69 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and cyclobutylmethyl bromide (0.223 g, 1.49 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4 The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoate (0.25 g) as a colorless liquid. A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoate (0.25 g, 0.49 mmol) and lithium hydroxide monohydrate (0.206 g, 4.9 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. Residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoic acid (0.106 g) as a white solid.1H-NMR (CDCl3, 400 MHz): 7.72 (d, 2H); 7.65 (d, 2H), 7.41 (s, 1H); 7.18 (s, 1H); 3.98 (q, 2H); 3.51 (t, 1H); 2.15-2.28 (m, 2H); 1.55-2.15 (m, 7H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.8 g, 1.8 mmol) was dissolved in anhydrous DMF (40 mL), NaH (60% wt. in paraffin oil, 0.052 g, 2.18 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and cyclopentyl bromide (0.298 g, 1.99 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×50 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetate (0.4 mg) as a thick liquid. A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetate (400 mg, 0.78 mmol) and lithium hydroxide monohydrate (0.330 g, 7.87 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetic acid (0.08 g).1H-NMR (CDCl3, 400 MHz): 12.5 (s, 1H), 7.84 (d, 2H); 7.70 (d, 2H), 7.55 (s, 1H); 7.35 (s, 1H); 4.22 (q, 2H); 3.3.35 (d, 1H); 1.82 (m, 1H); 1.18-1.68 (m, 7H); 1.08 (m, 1H). Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (0.6 g, 1.36 mmol) was dissolved in anhydrous DMF (30 mL), NaH (60% wt. in paraffin oil, 0.039 g, 1.36 mmol) was added at 0° C. The reaction mixture was stirred for 30 min at room temperature and cyclopentyl bromide (0.283 g, 1.49 mmol) was added drop wise at 0° C. The reaction mixture was stirred an additional 1 h at 0° C. and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by flash column chromatography to yield compound ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoate (0.29 g) as a colorless liquid. A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoate (400 mg, 0.719 mmol) and lithium hydroxide monohydrate (0.306 g, 7.29 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10 ml) was stirred for 3 h at room temperature. After completion of reaction volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoic acid (0.1 g).1H-NMR (CDCl3, 400 MHz): 7.55-7.78 (m, 4H); 7.42 (s, 1H), 7.18 (s, 1H); 6.92-7.16 (m, 4H); 3.98 (q, 2H); 3.84 (t, 1H); 3.41 (dd, 1H), 3.02 (dd, 1H). Cyclopropyl methanol (15 g, 207 mmol) was added to a stirred suspension of NaH (60% in mineral oil, 8.37 g) in 200 mL THF over a period of 15 min at 0° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h at RT. The mixture was cooled to 0° C. and a solution of 2,4-difluoro-1-nitrobenzene (30 g, 187 mmol) in 200 mL THF was added in a drop wise manner. The reaction mixture was stirred at 0° C. for 2 h and then poured onto ice water. The mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to give 22.0 g of 2-(cyclopropylmethoxy)-4-fluoro-1-nitrobenzene as an orange oil (86%). Diethyl malonate (9.8 g, 1.1 eq) was added to a stirred suspension of sodium hydride (60% in mineral oil, 2.09 g) in DMF (88 mL) over 15 min. at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. A solution of 2-cyclopropylmethoxy-4-fluoro-1-nitrobenzene (10 g, 1 eq) in DMF (88 mL) was added drop wise at 0° C., and the reaction mixture was heated to 100° C. for 3 h. The reaction mixture was allowed to cool to room temperature, poured into ice water and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL) and brine (100 mL), dried (MgSO4) and filtered. Evaporation of the volatiles under reduced pressure gave 10.0 g of crude product which was purified by chromatography over silica gel (hexane/EtOAc) gave of diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate (7.0 g).1H-NMR (CDCl3, 200 MHz): 0.4 (m, 2H), 0.71 (m, 2H), 1.3 (m, 1H), 1.3 (t, 6H), 3.96 (d, 2H), 4.25 (q, 4H), 4.5 (s, 1H), 7.02 (d, 1H), 7.18 (s, 1H), 7.81 (d, 2H). Compound diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate (10 g) was dissolved in 100 mL ethanol and cooled to 0° C., NaOH solution (4 eq) was added slowly to the reaction mixture for about 15 min. The reaction mixture was heated gently up to 60° C. for 5 h. Progress of the reaction was monitored by TLC analysis. After complete conversion of starting material solvent was evaporated under reduced pressure, residue dissolved in H2O, acidified with 6N HCl to pH-2. Filtered the solid material washed with water, dried under reduced pressure to give 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetic acid (6.5 g) as a yellow solid.1H-NMR (CDCl3, 200 MHz): 0.36 (m, 2H), 0.58 (m, 2H), 1.28 (m, 1H), 3.71 (s, 2H), 4.01 (d, 2H), 7.02 (d, 1H), 7.23 (s, 1H), 7.81 (d, 1H). 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetic acid (40 g, 143 mmol) was dissolved in 20% EtOH-HCl solution (200 ml) and refluxed for 3 h to convert the starting material to ester. The volatiles were removed under reduced pressure and the residue was extracted with ethyl acetate (×2). The combined organic extracts were washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude material was purified by re crystallization to ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (38 g) as pale yellow solid. To a stirred solution of compound ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (10 g), in dry MeOH (100 mL), Pd(OH)2 (2 g) was added and the mixture was reduced under an H2 atmosphere for 6 h at room temperature. The mixture was filtered a pad of Celite™ washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)acetate (7.5 g) as a thick liquid.1H-NMR (CDCl3, 200 MHz): 0.38 (m, 2H), 0.61 (m, 2H), 1.23 (m, 1H), 1.23 (t, 3H), 3.51 (s, 2H), 3.80 (d, 2H), 4.16 (q, 2H), 6.72 (m, 3H). To a stirred solution of ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)acetate (1.2 g, 4.0 mmol) in dry CCl4 (60 mL), NCS (0.427 g, 3.2 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature. The reaction mixture was diluted with water and extracted with DCM (2×50 mL). The combined organic layers were dried over Na2SO4, filtered and the volatiles removed in vacuo. The crude reaction mixture was purified by column chromatography to give ethyl 2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)acetate (920 mg) as a yellow solid. Ethyl-2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)-acetate (2.5 g, 10.0 mmol) was dissolved in a mixture of EtOH/H2O/H2SO4 (96%) 200 mL/400 mL/10 mL at 0° C. A solution of NaNO2 (3.2 g, 1.16 eq) in water (40 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min at the same temperature. A solution of KI (30 g, 30.1 mmol) in water (80 mL) was added drop wise at 0° C. The reaction mixture was heated to 50° C. for 2.5 h upon which the volatiles were removed under reduced pressure. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (300 mL) and brine (300 mL). The organic solution was dried over Na2SO4 and concentrated under reduced pressure to give a crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give the product ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate as a yellow oil (8.7 g). A mixture of compound ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate (5.1 g, 14 mmol), 4-trifluoromethylphenylboronic acid (3.36 g, 17 mmol), CsF (0.28 g, 1.84 mmol) and Pd (PPh3)4 (0.410 g, 0.4 mmol) in 75 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled to RT and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over NaSO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (4.6 g) as a yellow oil.1H-NMR (CDCl3, 200 MHz): 0.41 (m, 2H), 0.62 (m, 2H), 1.22 (t, 3H), 1.23 (m, 1H), 3.58 (s, 2H), 3.89 (d, 2H), 4.17 (q, 2H), 6.96 (m, 2H), 7.31 (s, 1H), 7.64 (m, 4H). Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (1.1 g, 2.4 mmol) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.9 g) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and cyclopropyl methyl bromide (1.25 mL) was added drop wise at 0° C. The reaction mixture was stirred for an additional 1 h at 0° C. upon which saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and the volatiles removed under reduced pressure to give 0.85 g of a colorless oil. The oil was dissolved in 10 mL of EtOH/H2O (9:1, v/v) and (1.0 g) LiOH added. The reaction mixture was refluxed for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 and evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3 cyclopropylpropanoic acid (0.42 g) as a white solid, L-21-1 (56%).1H NMR (300 MHz, CDCl3): δ 7.65 (d, 2H), 7.38 (d, 2H), 7.08 (s, 1H), 6.83 (s, 1H), 3.75 (d, 2H), 3.62 (t, 1H), 1.96 (m, 1H), 1.08 (m, 1H), 0.84 (m, 1H), 0.44 (m, 4H), 0.16 (m, 4H). Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (0.5 g,) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.13 g, mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,3-dibromopropane (1.5 mL) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and upon which saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give 240 mg of a colorless oil. The oil was dissolved in 10 mL of EtOH/H2O (9:1, v/v) and 0.42 g LiOH added. The reaction mixture was refluxed for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified via column chromatography over silica gel (hexane/EtOAc 9:1) to give 1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-cyclobutanecarboxylic acid (0.210 g) as a white solid (52% yield).1H NMR (300 MHz, CDCl3): δ 7.68 (d, 2H), 7.41 (d, 2H), 7.06 (s, 1H), 6.89 (s, 1H), 3.78 (d, 2H), 2.88 (m, 2H), 2.58 (m, 2H), 2.16 (m, 1H), 1.97 (m, 1H), 1.03 (m, 1H), 0.46 (m, 2H), 0.18 (m, 2H). Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (0.5 g) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.13 g, mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,4-dibromobutane (0.24 g) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give 380 mg of colorless oil. The oil was dissolved in 10 mL of EtOH/H2O (9:1, vvl) and 1.0 g LiOH added. The reaction mixture was refluxed for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4 filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-cyclopentanecarboxylic acid (0.210 g) as a white solid (60%).1H NMR (500 MHz, CDCl3): δ 7.68 (d, 2H), 7.41 (d, 2H), 7.16 (s, 1H), 6.91 (s, 1H), 3.78 (d, 2H), 2.66 (m, 2H), 1.97 (m, 2H), 1.79 (m, 4H), 1.03 (m, 1H), 0.46 (d, 2H), 0.18 (d, 2H). Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (5 g, 17.9 mmol) was dissolved in 50 mL anhydrous DMF, NaH (60% wt. in oil, 0.475 g, 19.7 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and cyclopropylmethyl bromide (2.67 g, 19.7 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 3-cyclopropyl-2-(3(cyclopropylmethoxy)-4-nitrophenyl)propanoate (4 g) as a colorless oil. To a stirred solution of ethyl 3-cyclopropyl-2-(3(cyclopropylmethoxy)-4-nitrophenyl)propanoate (4.0 g), in dry MeOH (100 mL), Pd(OH)2 (2 g) was added and the mixture was reduced under an atmosphere of H2 for 6 h at room temperature. The reaction mixture was filtered through a pad of Celite™ washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-3-cyclopropylpropanoate (3.5 g) as a thick liquid. To a stirred solution of ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-3-cyclopropylpropanoate (3.0 g, 9.8 mmol) in dry CHCl3 (50 mL), NBS (1.4 g, 7.8 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature. The reaction mixture was diluted with water and extracted with DCM (2×50 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to yield the ethyl 2-(4-amino-3-bromo-5-(Cyclopropylmethoxy)phenyl)-3-cyclopropyl propanoate (1.5 g) as a yellow solid. A mixture of ethyl 2-(4-amino-3-bromo-5-(Cyclopropylmethoxy)phenyl)-3-cyclopropyl propanoate (2.8 g, 7.2 mmol), 4-trifluoromethylphenylboronic acid (2.05 g, 18.8 mmol), CsF (2.19 g, 14.5 mmol) and Pd (PPh3)4 (0.837 g, 0.72 mmol) in 30 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled to RT, and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over NaSO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (2.5 g) as a yellow oil. Ethyl 2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (1 g, 2.2 mmol) was dissolved in a mixture of MeCN/H2O/HCl 30 mL/30 mL/2 mL at 0° C. A solution of NaNO2 (0.200 g, 2.9 mmol) in water (10 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.1 g, 11.1 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 90° C. for 2.0 h and the mixture was concentrated under reduced pressure. The reaction mixture was extracted with EtOAc (3×50 mL), the combined organic layers were washed with water (50 mL) followed by brine (50 mL), was dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude black oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (1.1 g) as a yellow oil. 2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (80 mg) was dissolved in 10 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and 57 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and then concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave compound 2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid (45 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.71 (d, 2H), 7.54 (d, 2H), 6.95 (d, 1H), 6.87 (s, 1H), 3.97 (d, 2H), 3.64 (t, 1H), 2.55 (m, 2H), 1.96 (m, 1H), 1.08 (m, 1H), 0.84 (m, 1H), 0.44 (m, 4H), 0.16 (m, 4H). Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (5 g, 17.9 mmol) was dissolved in 50 mL anhydrous DMF, NaH (60% wt. in oil, 1.43 g, 35.9 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,3-dibromopropane (1.91 mL, 17.9 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclobutanecarboxylate (2.8 g) as a colorless oil. To a stirred solution of ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclobutanecarboxylate (2.8 g), in dry MeOH (100 mL), Pd(OH)2 (1.2 g) was added and the reaction mixture was reduced under an atmosphere of H2 for 6 h at room temperature. The reaction mixture was filtered through a pad of Celite™ washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate (2.4 g) as a thick liquid. To a stirred solution of ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate (2.4 g, 8.3 mmol) in dry CHCl3 (50 mL), NBS (1.4 g, 7.8 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to yield ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate (1.5 g) as a yellow solid. A mixture of ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate (0.32 g, 0.86 mmol), 4-trifluoromethylphenylboronic acid (0.246 g, 1.3 mmol), CsF (0.262 g, 1.7 mmol) and Pd (PPh3)4 (0.1 g, 0.08 mmol) in 10 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled to RT and 25 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.290 g) as a yellow oil. Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.280 g, 0.64 mmol) was dissolved in a mixture of MeCN/H2O/HCl 10 mL/10 mL/4 mL at 0° C. A solution of NaNO2 (0.066 g, 0.96 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (0.32 g, 3.2 mmol) in water (2 mL) was added drop wise at 0° C. The reaction mixture was heated to 70° C. for 1 h and the solvent was evaporated under reduced pressure. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.110 g) as yellow oil. Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.1 g) dissolved in MeOH/THF/H2O (10 mL/10 mL/5 mL) and 70 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were dried over MgSO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid (75 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.71 (d, 2H), 7.54 (d, 2H), 6.86 (s, 1H), 6.85 (s, 1H), 3.97 (d, 2H), 2.85 (m, 2H), 2.54 (m, 2H), 2.13 (m, 1H), 1.92 (m, 1H), 1.35 (t, 1H), 0.47 (m, 2H), 0.41 (m, 2H). Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (0.5 g) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.13 g, mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,4-dibromobutane (0.24 g, mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclopentanecarboxylate (380 mg) as a colorless oil. To a stirred solution of ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclopentanecarboxylate (10 g), in dry MeOH (100 mL) Pd (OH)2 (2 g) was added and the mixture was reduced under an atmosphere of H2 for 6 h at room temperature. The mixture was filtered through a pad of Celite™, washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate (7.5 g) as a thick liquid. To a stirred solution of ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate (1.2 g, 4.0 mmol) in dry CCl4 (60 mL), NBS (0.427 g, 3.2 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to yield ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate (920 mg) as a yellow solid. A mixture of ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate (5.1 g, 14 mmol), 4-trifluoromethylphenylboronic acid (3.36 g, 17 mmol), CsF (0.28 g, 1.84 mmol) and Pd (PPh3)4 (0.410 g, 0.4 mmol) in 75 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (4.6 g) as a yellow oil. Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (1 g, 2.2 mmol) was dissolved in a mixture of MeCN/H2O/HCl 30 mL/30 mL/2 mL at 0° C. A solution of NaNO2 (0.200 g, 2.9 mmol) in water (10 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.1 g, 11.1 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 90° C. for 2.0 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude black oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate as yellow oil (1.1 g). Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (80 mg) dissolved in 10 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and 57 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylic acid (45 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.68 (d, 2H), 7.55 (d, 2H), 6.99 (s, 1H), 6.97 (s, 1H), 3.97 (d, 2H), 2.64 (m, 2H), 1.95 (m, 2H), 1.77 (m, 4H), 1.21 (m, 1H), 0.45 (m, 2H), 0.18 (m, 2H); Ethyl 2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)acetate (2 g, 6.5 mmol) was dissolved in 50 mL anhydrous DMF, NaH (60% wt. in oil, 0.171 g, 7.1 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and cyclopropylmethyl bromide (0.967 g, 7.16 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 3-cyclopropyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)propanoate (1.05 g) as a colorless oil. To a stirred solution of ethyl 3-cyclopropyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)propanoate (1.0 g), in dry MeOH (100 mL) Pd(OH)2 (500 mg) was added and the mixture was reduced under an atmosphere of H2 for 6 h at room temperature. The mixture was filtered off through a pad of Celite™, washing with MeOH. The combined filtrates were concentrated under reduced pressure to give ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (0.9 g) as a thick liquid. To a stirred solution of ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (0.9 g, 2.7 mmol) in dry CHCl3 (50 mL), NBS (0.412 g, 2.3 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to give ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.02 g) as a yellow solid. A mixture of ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.1, 3.3 mmol), 4-trifluoromethylphenylboronic acid (1.26 g, 6.7 mmol), CsF (1.26 g, 8.3 mmol) and Pd (PPh3)4 (0.38 g, 0.33 mmol) in 50 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 50 mL of EtOAc and 50 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.85 g, 82% yield) as a white solid. Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.85 g, 1.78 mmol) was dissolved in a mixture of MeCN/H2O/HCl 15 mL/15 mL/2 mL at 0° C. A solution of NaNO2 (0.185 g, 2.68 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.8 g, 17.8 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 90° C. for 2 h. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give an oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (0.528 g) as a yellow oil. The ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate (500 mg, 1.01 mmol) dissolved in 20 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and LiOH (57 mg) was added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclopropylpropanoic acid (250 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.72 (d, 2H), 7.54 (d, 2H), 7.02 (d, 2H), 4.44 (q, 2H), 3.72 (t, 1H), 1.92 (m, 1H), 1.79 (m, 1H), 1.08 (m, 1H), 0.66 (m, 1H), 0.44 (m, 2H), 0.16 (m, 2H). Ethyl 2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)acetate (3 g, 9.7 mmol) was dissolved in 50 mL anhydrous DMF, NaH (60% wt. in oil, 0.514 g, 10.7 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,3-dibromopropane (1.03 mL, 9.7 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (900 mg) as a colorless oil. To a stirred solution of ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (900 mg), in dry MeOH (50 mL), Pd(OH)2 (400 mg) was added and the mixture reduced under an atmosphere of H2 for 6 h at room temperature. The mixture was filtered through a pad of Celite™ washing with MeOH, the combined filtrates were concentrated under reduced pressure to yield ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (800 mg) as a thick liquid. To a stirred solution of ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (2.4 g, 8.3 mmol) in dry CHCl3 (50 mL), NBS (1.4 g, 7.8 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 hat room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents were dried over Na2SO4, filtered and concentrated under educed pressure. The crude reaction mixture was purified by column chromatography to give ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (1.5 g) as a yellow solid. A mixture of ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.32 g, 0.86 mmol), 4-trifluoromethylphenylboronic acid (0.246 g, 1.3 mmol), CsF (0.262 g, 1.7 mmol) and Pd (PPh3)4 (0.1 g, 0.08 mmol) in 10 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 25 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.290 g) as a yellow oil. Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.280 g, 0.64 mmol) was dissolved in a mixture of MeCN/H2O/HCl 10 mL/10 mL/4 mL at 0° C. A solution of NaNO2 (0.066 g, 0.96 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (0.32 g, 3.2 mmol) in water (2 mL) was added drop wise at 0° C. The reaction mixture was heated to 70° C. for 1 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated to give oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate as a yellow oil (0.110 g). Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate (0.1 g) dissolved in MeOH/THF/H2O (10 mL/10 mL/5 mL) and 70 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid (75 mg) of the product as a white solid.1H-NMR (500 MHz, CDCl3): 7.74 (d, 2H), 7.53 (d, 2H), 6.99 (s, 1H), 6.97 (s, 1H), 4.43 (q, 2H), 2.88 (m, 2H), 2.54 (m, 2H), 2.15 (m, 1H), 1.93 (m, 1H) Ethyl 2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)acetate (0.5 g, mmol) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.13 g, mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,4-dibromobutane (0.24 g, mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentane carboxylate (380 mg) as a colorless oil. To a stirred solution of ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentane carboxylate (10 g), in dry MeOH (100 mL) Pd(OH)2 (2 g) was added and reduced under an atmosphere of H2 for 6 h at room temperature. The mixture was filtered through a pad of Celite™ washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (7.5 g) as a thick liquid. To a stirred solution of ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (1.2 g, 4.0 mmol) in dry CCl4 (60 mL), NBS (0.427 g, 3.2 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to give ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (920 mg) as a yellow solid. A mixture of ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (5.1 g, 14 mmol), 4-trifluoromethylphenylboronic acid (3.36 g, 17 mmol), CsF (0.28 g, 1.84 mmol) and Pd(PPh3)4 (0.410 g, 0.4 mmol) in 75 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (4.6 g) as a yellow oil. Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate (1 g, 2.2 mmol) was dissolved in a mixture of MeCN/H2O/HCl 30 mL/30 mL/2 mL at 0° C. A solution of NaNO2 (0.200 g, 2.9 mmol) in water (10 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.1 g, 11.1 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 90° C. for 2.0 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give an oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give the ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylate (1.1 g) as yellow oil. The ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylate (80 mg) dissolved in 10 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and 57 mg LiOH added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentane carboxylic acid (45 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.74 (d, 2H), 7.55 (d, 2H), 7.08 (s, 1H), 4.44 (q, 2H), 2.66 (m, 2H), 1.98 (m, 2H), 1.78 (m, 4H). Ethyl 2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)acetate (4 g, 16.2 mmol) was dissolved in 50 mL anhydrous DMF and NaH (60% wt. in oil, 0.846 g, 21.1 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and isobutyl bromide (2.12 mL, 19.5 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 4-methyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)pentanoate (1.5 g) as a colorless oil. To a stirred solution of ethyl 4-methyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)pentanoate (1.5 g), in dry MeOH (100 mL), Pd(OH)2 (500 mg) was added and the mixture reduced under an atmosphere of H2 for 6 h at room temperature. The mixture was filtered through a pad of Celite™ washing with MeOH. The combined filtrates were concentrated under reduced pressure to give ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (1.2 g) as a thick liquid. To a stirred solution of ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.750 g, 2.2 mmol) in dry CHCl3 (100 mL), NBS (0.320 g, 1.8 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude reaction mixture was purified by column chromatography to give ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (700 mg) as a yellow solid. A mixture of ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.70 g, 1.6 mmol), 4-trifluoromethylphenylboronic acid (0.642 g, 3.39 mmol), CsF (0.641 g, 4.2 mmol) and Pd (PPh3)4 (0.196 g, 0.16 mmol) in 40 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 35 mL of EtOAc and 35 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (650 mg) as a colorless liquid. Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (640 mg, 1.3 mmol) was dissolved in a mixture of MeCN/H2O/HCl 15 mL/15 mL/1 mL at 0° C. A solution of NaNO2 (0.138 g, 2.0 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (1.32 g, 13.4 mmol) in water (5 mL) was added drop wise at 0° C. The reaction mixture was heated to 80° C. for 2 h and the mixture was concentrated under reduced pressure. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (50 mL) followed by brine (50 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give the ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (380 mg) as a yellow solid. Ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (320 mg, 0.647 mmol) was dissolved in a MeOH/THF/H2O (10 mL/10 mL/5 mL) mixture, LiOH (163 mg, 3.88 mmol) was added. The reaction mixture was stirred at room temperature for 5 h and then concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and evaporated under reduced pressure. Purification was achieved by re-crystallization in hexane/ether mixture to give 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (220 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.74 (d, 2H), 7.55 (d, 2H), 7.01 (s, 2H), 4.44 (q, 2H), 3.68 (t, 1H), 1.98 (m, 2H), 1.61 (m, 1H), 1.54 (m, 1H), 0.95 (d, 6H) To a stirred solution of ethyl 2-(4-hydroxyphenyl)acetate (25 g, 138 mmol) in 375 ml of DCM, sulfuryl chloride (9.48 mL 118 mmol) was slowly added at 0° C. over a period of 30 min. Diethyl ether (19.6 mL) was slowly added reaction mixture at 0° C. and stirring was continued for 30 min at 0° C. The reaction mixture was slowly warmed to 15° C. for 1 h. After completion of reaction, the mixture was poured onto crushed ice and extracted with DCM (×2). The combined organic layers were washed with 10% NaHCO3 solution followed by water. The organic layer was dried over Na2SO4, filtered and evaporated under vacuum to give compound ethyl 2-(3-chloro-4-hydroxyphenyl)acetate (15 g) as a thick oil. To a stirred solution of ethyl 2-(3-chloro-4-hydroxyphenyl)acetate (15 g, 69 mmol) in CCl4 (270 mL), bromine (11.1 g, 69 mmol) was added slowly (dissolved in 140 mL of CCl4) at −10° C. over a period of 30 min. The reaction mixture was stirred for another 1 h at −10° C. Upon completion of the reaction, the mixture was poured onto crushed ice and extracted with DCM (×2). The combined organic layers were washed with saturated Na2S2O3 solution, water, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was purified by re-crystallization using hexane to yield compound ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (7 g, 7 g starting material recovered) as a white solid. To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (6.5 g, 22 mmol), in DMF (100 mL), K2CO3 (7.67 g, 55.6 mmol) was added. Trifluoroethyl iodide (13.16 mL, 133 mmol) was added in a drop wise manner to the reaction mixture at RT. The mixture was then heated at 60° C. for 4 h. After completion of reaction, the mixture was poured into water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, dried over Na2SO4 and concentrated under reduced pressure. The crude compound was purified by column chromatography to give compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (6.5 g) as a white solid. To a suspension of NaH (0.327 g, 60% in paraffin oil, 8.1 mmol) in DMF (100 mL), slowly added a mixture of ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (3.0 g, 6.8 mmol) and cyclopropyl methylbromide (0.718 mL, 7.5 mmol) dissolved in DMF (20 mL) at 0° C. for 15 min under an atmosphere of nitrogen. The reaction mixture was allowed stir at 0° C. for 15 min, upon which the mixture was poured onto crushed ice and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, brine, dried over Na2SO4 and evaporated. The residue was purified by Flash column chromatography to give compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (2.35 g) as a thick syrup. A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-methyl phenylboronic acid (0.237 g, 1.74 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoate (375 mg,) as a thick oil. A mixture of ethyl 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoate (370 mg, 0.84 mmol) and lithium hydroxide monohydrate (282 mg, 6.7 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid (200 mg) as a white solid.1HNMR (CDCl3): 7.21-7.42 (m, 6H); 3.87 (q, 2H); 3.65 (t, 1H); 2.39 (s, 3H), 1.93 (m, 1H); 1.88 (m, 1H); 0.66 (m, 1H); 0.42 (m, 2H); 0.12 (m, 1H); 0.1 (m, 1H). A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-ethyl phenylboronic acid (225 mg, 1.74 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (400 mg) as a thick oil. A mixture of ethyl 2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (400 mg, 0.88 mmol) and lithium hydroxide monohydrate (222 mg, 5.2 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid (200 mg) as a white solid.1HNMR (CDCl3): 7.42 (d, 2H), 7.38 (s, 1H), 7.22 (d, 2H) 7.20 (s, 1H), 3.85 (q, 2H); 3.66 (t, 1H); 2.73 (q, 2H), 1.93 (m, 1H); 1.88 (m, 1H); 1.29 (t, 3H), 0.66 (m, 1H); 0.42 (m, 2H); 0.12 (m, 1H); 0.05 (m, 1H). A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-thiomethyl phenylboronic acid (293 mg, 1.7 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (360 mg) as a thick oil. A mixture of ethyl 2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (350 mg, 0.74 mmol) and lithium hydroxide monohydrate (186 mg, 4.44 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. Residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid (310 mg) as a white solid.1HNMR (CDCl3): 7.46 (d, 2H), 7.38 (s, 1H), 7.32 (d, 2H), 7.22 (s, 1H), 3.93 (q, 2H); 3.68 (t, 1H); 2.56 (s, 3H), 1.93 (m, 1H); 1.78 (m, 1H); 1.29 (t, 3H), 0.65 (m, 1H); 0.42 (m, 2H); 0.12 (m, 1H); 0.05 (m, 1H). A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-trifluoromethoxy phenylboronic acid (310 mg, 1.65 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (260 mg) as a thick oil. A mixture of ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (260 mg, 0.50 mmol) and lithium hydroxide monohydrate (186 mg, 4.44 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid (180 mg) as white solid.1HNMR (CDCl3): 7.56 (d, 2H), 7.40 (s, 1H), 7.25 (m, 3H), 3.98 (q, 2H); 3.68 (t, 1H); 2.56 (s, 3H), 1.913 (m, 1H); 1.76 (m, 1H); 1.29 (t, 3H), 0.62 (m, 1H); 0.41 (m, 2H); 0.12 (m, 1H); 0.05 (m, 1H). A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-isopropyl phenylboronic acid (225 mg, 1.74 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (400 mg) as thick oil. A mixture of ethyl 2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate (400 mg, 0.85 mmol) and lithium hydroxide monohydrate (215 mg, 5.1 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid (180 mg) as white solid.1HNMR (CDCl3): 7.44 (d, 2H), 7.38 (s, 1H), 7.31 (d, 2H) 7.21 (s, 1H), 3.86 (q, 2H); 3.67 (t, 1H); 2.98 (m, 1H), 1.93 (m, 1H); 1.78 (m, 1H); 1.28 (d, 6H), 0.66 (m, 1H); 0.43 (m, 2H); 0.12 (m, 1H); 0.05 (m, 1H). To a suspension of NaH (0.65 g, 60% in paraffin oil) in DMF (100 mL), slowly added a mixture of ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (3.0 g, 6.8 mmol) and 1,3-dibromo propane (1.61 g, 8.0 mmol) dissolved in DMF (20 mL) at 0° C. for 15 min under an atmosphere of nitrogen. The reaction mixture was allowed stir at 0° C. for 15 min, upon which the reaction mixture was poured onto crushed ice and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by Flash column chromatography to give ethyl 1-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (2.12 g) as a thick syrup. A mixture of compound ethyl 1-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (500 mg, 1.2 mmol), 4-methyl phenylboronic acid (0.237 g, 1.68 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutanecarboxylate (325 mg) as thick oil. A mixture of ethyl 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutanecarboxylate (300 mg, 0.70 mmol) and lithium hydroxide monohydrate (280 mg, 11.6 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid (185 mg, 66%) as white solid.1HNMR (CDCl3): 7.42 (m, 2H); 7.32 (s, 1H), 7.23 (d, 2H), 7.18 (s, 1H), 3.87 (q, 2H); 2.85 (m, 2H), 2.54 (m, 2H), 2.39 (s, 3H), 2.12 (m, 1H); 1.83 (m, 1H). A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (500 mg, 1.2 mmol), 4-ethyl phenylboronic acid (225 mg, 1.74 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 1-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (360 mg) as a thick oil. A mixture of ethyl 1-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (350 mg, 0.84 mmol) and lithium hydroxide monohydrate (222 mg, 9.2 mmol) in a MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid (260 mg) as white solid.1HNMR (CDCl3, 500 MHz): 7.42 (d, 2H), 7.38 (s, 1H), 7.22 (d, 2H) 7.20 (s, 1H), 3.85 (q, 2H); 2.82 (m, 2H), 2.71 (q, 2H), 2.52 (m, 2H), 2.15 (m, 1H), 1.91 (m, 1H); 1.27 (t, 3H). A mixture of ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (500 mg, 1.2 mmol), 4-thiomethyl phenylboronic acid (293 mg, 1.7 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (342 mg) as thick oil. A mixture of ethyl 1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (325 mg, 0.70 mmol) and lithium hydroxide monohydrate (186 mg, 4.44 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid (265 mg) as a white solid.1HNMR (CDCl3): 7.46 (d, 2H), 7.38 (s, 1H), 7.32 (d, 2H), 7.19 (s, 1H), 3.93 (q, 2H); 2.83 (m, 2H), 2.53 (s, 3H), 2.32 (m, 2H), 2.13 (m, 1H), 1.93 (m, 1H). A mixture of ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate (500 mg, 1.2 mmol), 4-isopropyl phenylboronic acid (245 mg, 1.68 mmol), Palladium Tetrakis (triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (425 mg) as thick oil. A mixture of ethyl 1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate (400 mg, 0.88 mmol) and lithium hydroxide monohydrate (215 mg, 5.1 mmol) in MeOH/THF/Water solvent mixture (10 ml/10 ml/10/ml) was stirred for 3 h at room temperature. After completion of the reaction, the volatiles were removed under reduced pressure. The residue was diluted with water, acidified with 5% HCl solution and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with water, dried with Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by Flash Column Chromatography to give 1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid (289 mg) as white solid.1HNMR (CDCl3): 7.44 (d, 2H), 7.38 (s, 1H), 7.31 (d, 2H) 7.21 (s, 1H), 3.86 (q, 2H); 2.99 (m, 1H), 2.86 (m, 2H), 2.52 (m, 2H), 2.13 (m, 1H), 1.92 (m, 1H); 1.28 (d, 6H). To a stirred solution of ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.2 g, 4.0 mmol) in dry CCl4 (60 mL), NCS (0.427 g, 3.2 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by column chromatography to yield compound ethyl-2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropyl propanoate (0.920 g) as a yellow solid. Ethyl-2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropyl propanoate (0.9 g, 2.6 mmol) was dissolved in a mixture of AcCN/H2O/HCl (96%) 25 mL/25 mL/1 mL at 0° C. A solution of NaNO2 (0.277 g, 4.02 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of KI (4.5 g, 26.8 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 70° C. for 1 h. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (100 mL) followed by brine (100 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl 2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.1 g, 90.9%) as yellow oil. A mixture of ethyl 2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (1.1 g, 2.4 mmol), 4-trifluoromethylphenylboronic acid (0.928 g, 4.9 mmol), CsF (0.926 g, 6.1 mmol) and Pd (PPh3)4 (0.283 g, 0.245 mmol) in 50 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 40 mL of EtOAc and 40 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow oil. The oil was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropyl propanoate (0.650 g) as a yellow oil. Ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropyl propanoate (0.65 g, 1.31 mmol) was dissolved in 25 mL of MeOH/THF/H2O (10:10:5, vvl), LiOH (0.252 g, 10.5 mmol) was added. The reaction mixture was stirred for 5 h at room temperature and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (DCM/MeOH, 95:5) gave the 2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropylpropanoic acid (0.585 g) as a white solid.1H NMR (500 MHz, CDCl3/TMS): δ 7.71 (d, 2H), 7.39 (d, 2H), 7.22 (s, 1H), 6.91 (s, 1H), 4.23 (q, 2H), 3.72 (t, 1H), 1.93 (m, 1H), 1.82 (m, 1H), 0.81 (m, 1H), 0.52 (m, 2H), 0.15 (m, 2H). To a stirred solution of ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (2.0 g, 6.3 mmol) in dry CHCl3 (30 mL), NCS (0.842 g, 6.3 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×100 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by Flash column chromatography to yield ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.4 g) as thick syrup. Ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.45 g, 1.27 mmol) was dissolved in a mixture of AcCN/H2O/HCl (96%) 15 mL/10 mL/3.1 mL at 0° C. A solution of NaNO2 (0.132 g, 1.91 mmol) in water (1 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of KI (2.11 g, 12.7 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 80° C. for 1 h. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (100 mL) followed by brine (100 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.350 g) as yellow oil. A mixture of ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.35, 7.35 mmol), 4-trifluoromethylphenylboronic acid (0.277 g, 1.47 mmol), CsF (0.277 g, 1.83 mmol) and Pd (PPh3)4 (0.084 g, 0.36 mmol) in 20 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 20 mL of EtOAc and 20 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutanecarboxylate (0.182 g) as a colorless oil. Ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutanecarboxylate (0.2 g, 0.41 mmol) was dissolved in 25 mL of MeOH/THF/H2O (10:10:5, vvl), LiOH (0.10 g, 4.1 mmol) was added. The reaction mixture was stirred for 5 h at room temperature and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (DCM/MeOH, 95:5) gave the compound 1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutanecarboxylic acid (0.06 g) as a white solid.1H NMR (500 MHz, CDCl3/TMS): δ 7.72 (d, 2H), 7.41 (d, 2H), 7.19 (s, 1H), 6.79 (s, 1H), 4.23 (q, 2H), 3.92 (m, 2H), 2.58 (m, 2H), 2.19 (m, 1H), 1.97 (m, 1H); To a stirred solution of ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (1.2 g, 3.6 mmol) in dry CHCl3 (60 mL), NCS (0.411 g, 3.08 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×100 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by Flash column chromatography to yield ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (0.860 g) as a thick syrup. Ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (0.86 g, 2.3 mmol) was dissolved in a mixture of AcCN/H2O/HCl (96%) 10 mL/8 mL/2.1 mL at 0° C. A solution of NaNO2 (0.243 g, 3.5 mmol) in water (1 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of KI (3.9 g, 23.5 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 80° C. for 1 h. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (100 mL) followed by brine (100 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (0.580 g) as pale yellow oil. A mixture of ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate (0.58, 1.2 mmol), 4-trifluoromethylphenylboronic acid (0.56 g, 2.4 mmol), CsF (0.46 g, 3.0 mmol) and Pd (PPh3)4 (0.14 g, 0.12 mmol) in 20 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 25 mL of EtOAc and 25 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentanecarboxylate (0.480 g) as a color less oil. Ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentane carboxylate (0.32 g, 0.64 mmol) was dissolved in 25 mL of MeOH/THF/H2O (10:10:5, vvl), LiOH (0.163 g, 3.88 mmol) was added. The reaction mixture was stirred for 5 h at room temperature and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (DCM/MeOH, 95:5) gave the 1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentanecarboxylic acid (0.220 g, 73%) as a white solid.1H NMR (500 MHz, CDCl3): δ 7.69 (d, 2H), 7.41 (d, 2H), 7.26 (s, 1H), 6.92 (s, 1H), 4.22 (q, 2H), 3.71 (m, 2H), 1.98 (m, 2H), 1.81 (m, 4H). To a stirred solution of ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.25 g, 0.75 mmol) in dry CHCl3 (20 mL), NCS (0.08 g, 0.6 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×100 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by Flash column chromatography to yield ethyl 2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.15 g) as thick syrup. Ethyl 2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.7 g, 1.9 mmol) was dissolved in a mixture of AcCN/H2O/HCl (96%) 20 mL/20 mL/1.3 mL at 0° C. A solution of NaNO2 (0.197 g, 2.8 mmol) in water (2 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of KI (3.16 g, 19.0 mmol) in water (10 mL) was added drop wise at 0° C. The reaction mixture was heated to 80° C. for 1 h. The reaction mixture was extracted with EtOAc (3×100 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (100 mL) followed by brine (100 mL). The solution was dried over Na2SO4, filtered and concentrated to give crude black oil which was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl-2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.35 g) as pale yellow oil. A mixture of ethyl-2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate (0.5, 1.04 mmol), 4-trifluoromethylphenylboronic acid (0.96 g, 2.09 mmol), CsF (0.395 g, 2.6 mmol) and Pd (PPh3)4 (0.121 g, 0.104 mmol) in 50 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 25 mL of EtOAc and 25 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by column chromatography over silica gel (hexane/EtOAc, 95:5) to give ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoate (0.265 g,) as a colorless oil. Ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoate (0.35 g, 0.733 mmol) was dissolved in 25 mL of MeOH/THF/H2O (10:10:5, vvl), LiOH (0.176 g, 7.33 mmol) was added. The reaction mixture was stirred for 5 h at room temperature and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over Na2SO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (DCM/MeOH, 95:5) gave the compound 2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoic acid (0.085 g) as a white solid.1H NMR (500 MHz, CDCl3): δ 7.69 (d, 2H), 7.41 (d, 2H), 7.20 (s, 1H), 6.86 (s, 1H), 4.23 (q, 2H), 3.71 (t, 1H), 2.01 (m, 1H), 1.73 (m, 1H), 1.58 (m, 1H), 0.98 (d, 6H). Cyclopropylmethanol (15 g, 207 mmol) was added to a stirred suspension of NaH (60% in mineral oil, 8.37 g) in 200 mL THF over 15 min at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. A solution of 2,4-difluoro-1-nitrobenzene (30 g, 187 mmol) in 200 mL THF was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 2 h and then poured into ice water. The reaction mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to give 22.0 g of product as orange oil (86%). Diethyl malonate (9.8 g, 1.1 eq.) was added to a stirred suspension of sodium hydride (60% in mineral oil, 2.09 g) in 88 mL DMF over 15 min. at 0° C. under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. A solution of 2-cyclopropylmethoxy-4-fluoro-1-nitrobenzene (10 g, 1 eq.) in DMF (88 mL) was added drop wise at 0° C., and the reaction mixture was heated to 100° C. for 3 h. The reaction mixture was allowed to cool to room temperature, poured into ice water and extracted with EtOAc (3×100 mL). The combined organic phases were washed with water (3×100 mL), brine (100 mL) and dried (MgSO4). Evaporation of solvent under reduced pressure gave 10.0 g of crude product which was purified by silica gel chromatography (hexane/EtOAc) gave 7.0 g of the desired product (42%) 1H-NMR (CDCl3, 200 MHz): 0.4 (m, 2H), 0.71 (m, 2H), 1.3 (m, 1H), 1.3 (t, 6H), 3.96 (d, 2H), 4.25 (q, 4H), 4.5 (s, 1H), 7.02 (d, 1H), 7.18 (s, 1H), 7.81 (d, 2H). i) Diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate (10 g) was dissolved in 100 mL ethanol and cooled to 0° C., NaOH solution (4 eq) was added slowly to the reaction mixture for about 15 min. The reaction mixture was heated gently up to 60° C. for 5 h. Progress of the reaction was monitored by TLC analysis. After complete conversion of starting material solvent was evaporated under reduced pressure, the residue dissolved in H2O, acidified with 6N HCl to pH-2. The solid material was collected via filtration, washed with water, dried under reduced pressure to yield 6.5 g (90%) of 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetic acid as a yellow solid. 1H-NMR (CDCl3, 200 MHz): 0.36 (m, 2H), 0.58 (m, 2H), 1.28 (m, 1H), 3.71 (s, 2H), 4.01 (d, 2H), 7.02 (d, 1H), 7.23 (s, 1H), 7.81 (d, 1H). ii) 2-(3-(Cyclopropylmethoxy)-4-nitrophenyl)acetic acid (6.5 g) was taken up in an ethanolic HCl solution (50 mL, 25%) and refluxed for 4 h, monitored by TLC. The reaction mixture was concentrated in vacuo to dryness and dissolved in ethyl acetate. The mixture was washed with NaHCO3 solution, dried over NaSO4 and concentrated in vacuo to give crude yellow solid which was purified by recrystallization to give the desired product (4.2 g). 1H-NMR (CDCl3, 200 MHz): 0.36 (m, 2H), 0.58 (m, 2H), 1.12 (t, 3H), 1.28 (m, 1H), 3.71 (s, 2H), 4.01 (d, 2H), 4.21 (q, 2H), 7.02 (d, 1H), 7.23 (s, 1H), 7.81 (d, 1H). To a stirred solution of ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (10 g), in dry MeOH (100 mL) was added Pd(OH)2 (2 g). The mixture was hydrogenated under a H2 atmosphere for 6 h at room temperature. The reaction mixture was filtered through a pad of Celite™, washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield 7.5 g of the desired product as an oil. 1H-NMR (CDCl3, 200 MHz): 0.38 (m, 2H), 0.61 (m, 2H), 1.23 (m, 1H), 1.23 (t, 3H), 3.51 (s, 2H), 3.80 (d, 2H), 4.16 (q, 2H), 6.72 (m, 3H). To a stirred solution of ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)acetate (1.2 g, 4.0 mmol) in dry CCl4 (60 mL), NCS (0.427 g, 3.2 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 h at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by column chromatography to yield Ethyl 2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)acetate (920 mg) as a yellow solid. Ethyl-2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)-acetate (2.5 g, 10.0 mmol) was dissolved in a mixture of AcCN/H2O/HCl (96%) 50 mL/50 mL/25 mL at 0° C. A solution of NaNO2 (3.2 g, 1.16 eq) in water (40 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of KI (30 g, 30.1 mmol) in water (80 mL) was added drop wise at 0° C. The reaction mixture was heated to 50° C. for 2.5 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with 10% sodium thiosulfate (2×50 mL), water (300 mL) followed by brine (300 mL). The solution was dried over Na2SO4, filtered and concentrated in vacuo to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give the ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate (1.2 g) A mixture of compound ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate (5.1 g, 12.9 mmol), 4-trifluoromethylphenylboronic acid (3.66 g, 19 mmol), CsF (3.9 g, 25.8 mmol) and Pd (PPh3)4 (1.5 g, 1.3 mmol) in 100 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by column chromatography over silica gel (hexane/EtOAc) to give ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (3.2 g) as yellow oil. Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (0.5 g, 1.2 mmol) was dissolved in 10 mL anhydrous DMF, NaH (60% wt. in oil, 0.058 g, 2.4 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,3-dibromopropane (1.5 mL) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give a (320 mg) of colorless oil. The oil was dissolved in 10 mL of EtOH/H2O (9:1, vvl) and 0.163 g LiOH added. The reaction mixture was refluxed for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) gave 1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutane carboxylic acid (0.210 g) as a white solid.1H NMR (300 MHz, CDCl3): δ 7.68 (d, 2H), 7.41 (d, 2H), 7.06 (s, 1H), 6.78 (s, 1H), 3.78 (d, 2H), 2.86 (m, 2H), 2.58 (m, 2H), 2.16 (m, 1H), 1.95 (m, 1H), 1.03 (m, 1H), 0.46 (m, 2H), 0.18 (m, 2H). Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate (0.5 g,) was dissolved in 10 mL anhydrous DMF and NaH (60% wt. in oil, 0.058 g, 2.4 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and 1,4-dibromobutane (0.24 g) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give a (320 mg, 0.64 mmol) of colorless oil. The oil was dissolved in 10 mL of EtOH/H2O (9:1, vvl) and LiOH (0.163 g, 3.88 mmol) added. The reaction mixture was refluxed for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc 9:1) to give 1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentane carboxylic acid (220 mg) as a white solid.1H NMR (500 MHz, CDCl3): δ 7.68 (d, 2H), 7.41 (d, 2H), 7.16 (s, 1H), 6.91 (s, 1H), 3.78 (d, 2H), 2.66 (m, 2H), 1.97 (m, 2H), 1.79 (m, 4H), 1.03 (m, 1H), 0.46 (d, 2H), 0.18 (d, 2H); Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate (2.2 g, 7.8 mmol) was dissolved in 20 mL anhydrous DMF and NaH (60% wt. in oil, 0.189 g, 7.8 mmol) was added at 0° C. The reaction mixture was stirred for 0.5 h at 25° C. and isobutyl bromide (1.08 g, 7.8 mmol) was added drop wise at 0° C. The reaction mixture was stirred at 0° C. for 1 h and saturated NH4Cl solution (10 mL) was added. The reaction mixture was extracted with EtOAc (3×20 mL) and the combined organic phases were washed with water (3×20 mL) and brine (20 mL), and dried over MgSO4, filtered and concentrated under reduced pressure to give ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)-4-methylpentanoate (2.06 g) of colorless oil. To a stirred solution of ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)-4-methylpentanoate (2.0 g, 5.9 mmol), in dry MeOH (50 mL) Pd(OH)2 (1.1 g) was added. The mixture was reduced under an atmosphere of H2 for 6 h at room temperature. The reaction mixture was filtered off through a pad of Celite™, washing with MeOH. The combined filtrates were concentrated under reduced pressure to yield ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (1.69 g) as a thick liquid. To a stirred solution of ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (1.65 g, 5.4 mmol) in dry CCl4 (60 mL), NBS (0.96 g, 5.4 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×50 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by column chromatography to yield ethyl 2-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (1.5 g) as a yellow solid. A mixture of ethyl 2-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (1.5 g, 3.9 mmol), 4-trifluoromethylphenylboronic acid (1.1 g, 5.8 mmol), CsF (1.47 g, 7.8 mmol) and Pd (PPh3)4 (0.45 g, 0.39 mmol) in 75 mL anhydrous 1,2-dimethoxy ethane was refluxed for 8 h under argon. The reaction mixture was cooled, and 75 mL of EtOAc and 75 mL of water were added. The organic phase was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to yellow oil. The oil was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl-2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methyl pentanoate (1.2 g) as a yellow oil. Ethyl-2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methyl pentanoate (0.2 g, 0.44 mmol) was dissolved in a mixture of AcCN/H2O/HCl 10 mL/10 mL/1 mL at 0° C. A solution of NaNO2 (0.039 g, 0.53 mmol) in water (1 mL) was added drop wise at 0° C., and the reaction mixture was stirred for 40 min, at the same temperature. A solution of CuCl (0.22 g, 2.2 mmol) in water (5 mL) was added drop wise at 0° C. The reaction mixture was heated to 40° C. for 2.0 h and the solvent was evaporated. The reaction mixture was extracted with EtOAc (3×50 mL), and the combined organic layers were washed with water (30 mL) followed by brine (20 mL). The solution was dried over Na2SO4, filtered and concentrated in vacuo to give crude black oil which was purified by chromatography over silica gel (hexane/EtOAc) to give ethyl-2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.12 g) as a thick oil. The ethyl-2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (120 mg, 0.255 mmol) dissolved in 10 mL of MeOH/THF/H2O (10 mL/10 mL/5 mL) and LiOH (30 mg, 1.2 mmol) was added. The reaction mixture was stirred at room temperature for 5 h and concentrated under reduced pressure. Water (10 mL) was added and the reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phases were dried over MgSO4, filtered and evaporated under reduced pressure. Purification by column chromatography over silica gel (DCM:MeOH 9:1) gave 2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (89 mg) as a white solid.1H-NMR (500 MHz, CDCl3): 7.68 (d, 2H), 7.55 (d, 2H), 6.92 (s, 1H), 6.85 (s, 1H), 3.96 (d, 2H), 3.64 (t, 1H), 1.98 (m, 1H), 1.68 (m, 1H), 1.55 (m, 1H), 1.32 (m, 1H), 0.91 (d, 6H), 0.64 (m, 2H), 0.42 (m, 2H); To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (12 g, 40.816 mmol) in DMSO (80 mL) were added K2CO3 (14.08 g, 102.020 mmol) and cyclopropylmethylbromide (5 mL, 4.880 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 80° C. temperature over a period of 14 h. After completion of starting material (by TLC), the reaction mixture was cooled to RT and quenched with water and extracted with EtOAc (3×100 mL). Combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate (10 g) yellow solid. To a stirred solution of NaH (0.3 g, 12.5 mmol) in DMF (10 mL) was added ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate (2.0 g, 5.70 mmol) at 0° C. The reaction mixture was stirred at 0° C. over a period of 30 min. To the reaction mixture was added 2-bromo ethyl methyl ether (0.87 g, 6.25 mmol) and stirred at 0° C. for 30 min. After completion of starting material (by TLC), the reaction mixture was diluted with water (20 mL), acidified with 1N HCl (pH=5) and extracted with EtOAc (3×50 mL). Combined organic layers were washed with water (3×25 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methoxybutanoate (560 mg) as an off white solid. To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methoxybutanoate (2.3 g, 5.660 mmol) in a mixture of DMF (50 mL) and water (5 mL) were added Cs2CO3 (6.4 g, 19.815 mmol), Pd(TPP)4 (1.3 g, 1.120 mmol) and 4-(trifluoromethyl)phenyl boronic acid (1.29 g, 6.780 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), filtered off the catalyst and celite bed was washed with EtOAc and extracted with EtOAc (3×100 mL). Combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoate (1.2 g) as an off white solid. To a stirred solution of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoate (0.3 g, 0.638 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (53 mg, 12.030 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (20 mL), brine (30 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography to afford 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoic acid (100 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ ppm 7.68 (m, 4H), 7.40 (s, 1H), 7.20 (s, 1H), 3.80 (t, 1H), 3.41 (d, 2H), 3.25 (m, 5H), 2.39 (m, 1H), 1.99 (m, 1H), 0.95 (m, 1H), 0.4 (d, 2H), 0.0 (m, 2H). To a stirred solution of NaH (0.76 g, 15.82 mmol) in DMF (50 mL) was added compound 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoic acid (5.0 g, 14.4 mmol) at 0° C. The reaction mixture was stirred at 0° C. over a period of 30 min. To the reaction mixture was added isobutyl bromide (2.93 g, 21.57 mmol) and stirred at 0° C. for 1 h. After completion of starting material (by TLC), diluted with water (40 mL), acidified with 1N HCl (pH=5) and extracted with EtOAc (3×100 mL). Combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methyl pentanoate (5.0 g) as a liquid. To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methyl pentanoate (0.5 g, 1.239 mmol) in a mixture of DMF (10 mL) and water (5 mL) were added Cs2CO3 (1.4 g, 4.325 mmol), Pd (TPP)4 (286 mg, 2.475 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole (355 mg, 1.363 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), the solids were removed via filtration through a bed of Celite™ was washing with EtOAc (3×100 mL). The combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to afford ethyl 2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (100 mg) as an off white solid. To a stirred solution of ethyl 2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.1 g, 0.218 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (45 mg, 1.090 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography to afford 2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid (39 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 9.05 (s, 1H), 8.2 (m, 2H), 7.73 (m, 1H), 7.40 (s, 1H), 7.30 (s, 1H), 3.63 (t, 1H), 3.40 (d, 2H), 1.99 (m, 1H), 1.65 (m, 1H), 1.55 (m, 1H), 0.93 (m, 7H), 0.38 (d, 2H), −0.5 (d, 2H). To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.5 g, 1.240 mmol) in a mixture of DMF (20 mL) and water (5 mL) were added Cs2CO3 (1.4 g, 4.342 mmol), Pd(TPP)4 (286 mg, 2.480 mmol) and 5-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[c][1,2,5]oxadiazole (355 mg, 1.364 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), the solids were removed via filtration through a bed of Celite™ was washing with EtOAc (3×100 mL). The combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to afford ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (250 mg) as an off white solid. To a stirred solution of ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.25 g, 0.565 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (118.7 mg, 2.828 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography to afford compound-2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid (152 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.92 (s, 1H), 7.85 (m, 1H), 7.72 (m, 1H), 7.46 (s, 1H), 7.25 (s, 1H), 3.65 (t, 1H), 3.48 (d, 2H), 1.95 (m, 1H), 1.65 (m, 1H), 1.55 (m, 1H), 1.22 (m, 1H0, 0.93 (d, 6H), 0.39 (d, 2H), 0.0 (m, 2H). To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.5 g, 1.239 mmol) in a mixture of DMF (10 mL) and water (5 mL) were added Cs2CO3 (1.4 g, 4.325 mmol), Pd(TPP)4 (286 mg, 2.475 mmol) and 5-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[c][1,2,5]thiazdiazole (355 mg, 1.363 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), the solids were removed via filtration through a bed of Celite™ was washing with EtOAc (3×100 mL). The combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to afford ethyl 2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (222 mg) as an off white solid. To a stirred solution of ethyl 2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate (0.22 g, 0.479 mmol) in a mixture of THF (5 mL), methanol (5 mL) and water (2 mL) was added LiOH.H2O (60.3 mg, 1.438 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography to afford 2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methyl pentanoic acid (105 mg, 50.0%) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 8.18 (s, 1H), 8.03 (d, 1H), 7.96 (d, 1H), 7.42 (s, 1H), 7.18 (s, 1H), 3.68 (t, 1H), 3.43 (d, 2H), 2.00 (m, 1H), 1.70 (m, 1H), 1.58 (m, 1H), 0.98 (d, 6H), 0.88 (m, 1H), 0.38 (d, 2H), 0.0 (m, 2H). To a stirred compound ethyl 2-(3-bromo-4-hydroxyphenyl)-4-methylpentanoate (1.0 g, 3.174 mmol) in DCM (15 ml) chlorosulfonicacid (2 mL, 28.571 mmol) was added. The reaction mixture was stirred for 14 h at 80° C. under N2 atmosphere. After completion of starting material (by TLC), the reaction mixture was quenched with NaHCO3 solution and extracted with DCM (3×100 mL). Combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4, filtered and concentrated in vacuo to give ethyl 2-(3-bromo-5-(chlorosulfonyl)-4-hydroxyphenyl)-4-methyl pentanoate (0.5 g) as a liquid. To a stirred solution of ethyl 2-(3-bromo-5-(chlorosulfonyl)-4-hydroxyphenyl)-4-methyl pentanoate (0.73 g, 1.765 mmol) in THF (20 mL) was added N,N-dimethylamine solution (5.2 mL, 10.592 mmol) at RT under inert atmosphere. The reaction mixture was stirred at RT over a period of 14 h. After completion of starting material (by TLC), the reaction mixture was quenched with water and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-5-(N,N-dimethylsulfamoyl)-4-hydroxyphenyl)-4-methylpentanoate (0.6 g) as a pale yellow liquid. To a stirred solution of ethyl 2-(3-bromo-5-(N,N-dimethylsulfamoyl)-4-hydroxyphenyl)-4-methylpentanoate (0.75 g, 1.77 mmol) in DMSO (25 mL) were added K2CO3 (367 mg, 2.106 mmol) and cyclopropylmethylbromide (0.2 mL, 2.13 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 80° C. temperature over a period of 14 h. After completion of starting material (by TLC), the reaction mixture was cooled to RT and quenched with water and extracted with EtOAc (3×100 mL). Combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4. After filtration and evaporation, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-4-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)phenyl)-4-methylpentanoate (350 mg) as a liquid. To a stirred solution of 2-(3-bromo-4-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)phenyl)-4-methylpentanoate (0.5 g, 1.049 mmol) in a mixture of DMF (10 mL) and water (5 mL) were added Cs2CO3 (1.19 g, 3.670 mmol), Pd(TPP)4 (243 mg, 0.209 mmol) and 4-(trifluoromethyl)phenylbornate (220 mg, 1.150 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), filtered off the catalyst and celite bed was washed with EtOAc and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration in vacuo, the crude material was purified by column chromatography to afford 2-(6-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (100 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.83 (s, 1H), 7.72 (m, 4H), 7.51 (s, 1H), 3.73 (m, 1H), 3.38 (d, 2H), 2.95 (s, 3H), 2.87 (s, 3H), 2.01 (m, 1H), 1.65 (m, 1H), 1.51 (m, 1H), 0.91 (m, 7H), 0.40 (d, 2H), 0.00 (m, 2H). To a stirred solution of ethyl 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (1.0 g, 2.227 mmol) in a mixture of HCl: H2O (0.81 mL, 6.681 mmol) was added NaNO2 (0.180 g, 2.672 mmol). After being stirred for 1 h at 0° C. then added KI (3.69 g, 22.271 mmol) at 0° C. under inert atmosphere. The reaction mixture was stirred at 100° C. temperature over a period of 2 h. After completion of starting material (by TLC), the reaction mixture was cooled to RT and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4. After filtration and concentration in vacuo, the crude material was purified by column chromatography to afford ethyl 2-(6-(cyclopropylmethoxy)-5-iodo-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.93 g) as a solid. To a stirred solution of ethyl 2-(6-(cyclopropylmethoxy)-5-iodo-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.25 g, 0.447 mmol) in NMP (10 mL) was added CuCN (50 mg, 0.536 mmol) at RT under inert atmosphere. The reaction mixture was stirred at 200° C. temperature over a period of 2 h. After completion of starting material (by TLC), the reaction mixture was cooled to RT and extracted with EtOAc (3×20 mL). Combined organic layers were washed with water (3×15 mL), brine and dried over Na2SO4. After filtration and evaporation, the crude material was purified by column chromatography to afford ethyl 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.125 g) a solid. To a stirred solution of ethyl 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.125 g, 0.272 mmol) in a mixture of THF (5 mL), methanol (5 mL) and water (2 mL) was added LiOH.H2O (34 mg, 0.816 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by column chromatography to afford 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (50 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.70 (m, 4H), 7.61 (s, 1H), 7.51 (s, 1H), 3.71 (t, 1H), 3.55 (m, 2H), 2.00 (m, 1H), 1.67 (m, 1H), 1.51 (m, 1H), 1.02 (m, 1H), 0.91 (d, 6H), 0.45 (m, 2H), 0.05 (m, 2H). To a stirred solution of ethyl 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (1.0 g, 2.604 mmol) in a mixture of HCl: H2O (0.86 mL, 10.4 mmol) and THF (10 mL) was added NaNO2 (0.215 g, 3.92 mmol). After being stirred for 1 h at 0° C. then added NaSMe (368 mg, 0.260 mmol) at 0° C. under an inert atmosphere. The reaction mixture was stirred at RT over a period of 14 h. After complete consumption of starting material (by TLC), the reaction mixture was extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (3×75 mL), brine and dried over Na2SO4. After filtration and concentration under vacuo, the crude material was purified by column chromatography to afford ethyl 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (0.93 g) as a solid. To a stirred solution of ethyl 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate (80 mg, 0.166 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (20 mg, 0.832 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under vacuo. The crude material was purified by column chromatography to afford 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid (38 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.75 (d, 2H), 7.65 (d, 2H), 7.31 (s, 1H), 7.23 (s, 1H), 3.65 (t, 1H), 3.60 (d, 2H), 2.82 (s, 3H), 1.98 (m, 1H), 1.65 (m, 1H), 1.5 (m, 1H), 1.22 (m, 1H), 0.9 (d, 6H), 0.38 (d, 2H), 0.01 (d, 2H). To a stirred solution of NaH (40 mg, 0.830 mmol) in DMF (5 mL) was added compound ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (300 mg, 0.728 mmol) and stirred at 0° C. for 1 h. To the reaction mixture at 0° C. was added isopropyl bromide (0.08 mL, 0.880 mmol) and continued stirring at 0° C. over a period of 30 min. After complete consumption of the starting material (by TLC), the reaction mixture was diluted with water (20 mL), acidified with 1N Hcl (pH=5) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (3×15 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration under educed pressure, the crude material was purified by column chromatography to afford ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-3-methylbutanoate (120 mg) as a liquid. To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-3-methylbutanoate (0.12 g, 0.260 mmol) in a mixture of THF (5 mL), methanol (5 mL) and water (2 mL) was added LiOH.H2O (75 mg, 1.320 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of the starting material, as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL); combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The crude material was purified by column chromatography to afford ethyl2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-methylbutanoate (100 mg) as an off white solid.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.66 (m, 4H), 7.41 (s, 1H), 7.20 (s, 1H), 3.41 (d, 2H), 3.15 (d, 1H), 2.3 (m, 1H), 1.12 (d, 3H), 0.97 (m, 1H), 0.72 (d, 3H), 0.40 (d, 2H), 0.00 (d, 2H). To a stirred solution of NaH (64 mg, 0.13 mmol) in DMF (15 mL) was added ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate (500 mg, 0.12 mmol) and 1,1,1-trifluoro-2-iodoethane (0.304 mL, 0.15 mmol) at 0° C. The reaction mixture was stirred at 0° C. over a period of 30 min. After completion of starting material (by TLC), diluted with water (20 mL), acidified with 1N HCl (pH=5) and extracted with EtOAc (3×30 mL). Combined organic layers were washed with water (3×15 mL), brine and dried over anhydrous Na2SO4. After filtration and evaporation, the crude material was purified by column chromatography to afford ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate (300 mg) as liquid. To a stirred solution of ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate (0.1 g, 0.404 mmol) in a mixture of THF (10 mL), methanol (10 mL) and water (5 mL) was added LiOH.H2O (85 mg, 2.024 mmol) at room temperature and the mixture was stirred at RT for 2 h. After complete consumption of the starting material as monitored by TLC, the reaction mixture was diluted with water (10 mL) and acidified using 1 N HCl at 0° C. The aqueous layer was extracted with EtOAc (2×20 mL) the combined organic extracts were washed with water (10 mL), brine (20 mL), dried over anhydrous Na2SO4 and evaporated under vacuum. The crude material was purified by column chromatography to 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid (38 mg) as sticky syrup.1HNMR (500 MHz) (CDCl3): δ (ppm) 7.71 (m, 4H), 7.39 (s, 1H), 7.19 (s, 1H), 3.92 (m, 1H), 3.41 (d, 2H), 3.08 (m, 1H), 2.54 (m, 1H), 0.96 (m, 1H), 0.40 (d, 2H), 0.00 (m, 2H). The following examples can also be made using analogous procedures as described previously, substituting the appropriate reagents known to those of ordinary skill in the art. The following examples can also be made using analogous procedures as described previously, substituting the appropriate reagents known to those of ordinary skill in the art. Examples 464, 474, 480, 481, 483, 485, 488, 489, 494, 504, 1292, 1334, 2490, 2708, 3211, 3212, 3213, 3214, 3215, 3216 and 3217 The Aβ peptide is proteolytically derived from a larger integral membrane amyloid precursor protein (APP). The production of Aβ is derived from proteolytic cleavages at its N- and C-termini within β-APP by the β and γ-secretase activities, respectively. Transfected cells overexpressing β-APP or its equivalent producing the Aβ peptide can be used to monitor the effects of synthetic compounds on the production of Aβ. To analyze a compound's effects on the concentrations of the various products of the γ-secretase cleavage activity, the Aβ peptides, various methods known to a person skilled in the art are available. Examples of such methods, but not limited to, include mass-spectrometric identification as described by Wang et al, 1996, J. Biol. Chem. 271:31894-31902) or detection by specific antibodies using, for example, ELISA's. Examples of such assays for measuring the production of Aβtotal, Aβ40 and Aβ42 by ELISA include but are not limited to those described by Vassar et al., 1999, Science 286:735-741. Suitable kits containing the necessary antibodies and reagents for such an analysis are available, for example, but not limited to the Genetics Company, Wako, Covance, and Innogenetics. The kits are essentially used according to the manufacturers recommendations similar to the assay that is described by Citron et al., (1997) Nature Medicine 3:67-72 and the original assay described by Seubert et al., (1992) Nature 359:325-327. Screening was carried out using the human embryonic kidney cell line HEK-293 overexpressing an amyloid precursor protein (APP) transgene grown in Pro-293a CDM media (BioWhittaker). Cells were grown to approximately 70-80% confluency subsequent to the addition of test compounds. The growth media was aspirated or removed, the cells washed, and replaced with 100 μl of compound, appropriately diluted in serum free media. The plates are then incubated for 16-18 hours at 37° C. Conditioned Medium samples are removed for analysis/quantitation of the various Aβ peptide levels by differential ELISA's as described in accompanying instructions to the kits. Those compounds examined which do not demonstrate any overt toxicity or non-specific inhibitory properties are investigated further for their Aβ inhibitory effects and form the basis of medicinal chemistry efforts and to study the effect of the compounds in different experimental conditions and configurations. Table 14 shows representative in vitro data (HEK 293) EC50 data for compounds of the disclosure where: A indicates a compound has an EC50 for lowering Aβ342 of <1 μM
Table 15 shows individual EC50 values for representative compounds of the disclosure. Rat primary neocortical cultures are established through the dissection of the neocortices from 10-12 E17 embryos harvested from time-pregnant SD (Sprague Dawley) rats (Charles River Laboratories). Following dissection, the combined neocortical tissue specimen volume is brought up to 5 mL with dissection medium (DM; 1×HBSS (Invitrogen Corp., cat#14185-052)/10 mM HEPES (Invitrogen Corp., cat#15630-080)/1 mM Sodium Pyruvate (Invitrogen Corp., cat#11360-070)) supplemented with 100 uL Trypsin (0.25%; Invitrogen Corp., cat#15090-046) and 100 uL DNase I (0.1% stock solution in DM, Roche Diagnostics Corp., cat#0104159), undergoing digestion via incubation at 37° C. for 10 minutes. Digested tissue is washed once in plating medium (PM; NeuroBasal (Invitrogen Corp., cat#21103-049)/10% Horse Serum (Sigma-Aldrich Co., cat#H1138)/0.5 mM L-Glutamine (Invitrogen Corp., cat#25030-081)), then resuspended in a fresh 10 mL PM volume for trituration. Trituration consists of 18 cycles with a 5 mL-serological pipet, followed by 18 cycles with a flame-polished glass Pasteur pipet. The volume is elevated to 50 mL with PM, the contents then passed over a 70 um cell-strainer (BD Biosciences, cat#352350) and transferred directly to a wet-ice bath. The cell-density is quantified using a hemacytometer, and diluted to allow for the plating of 50000 cells/well/100 uL in pre-coated 96-well PDL-coated plates (Corning, Inc., cat#3665). Cells are incubated for 4-5 hours at 37° C./5% CO2, after which time the entire volume is exchanged to feeding medium (FM; NeuroBasal/2% B-27 Serum-free supplement (Invitrogen Corp., cat#17504-044)/0.5 mM L-Glutamine/1% Penicillin-Streptomycin (Invitrogen Corp., cat#15140-122)). The cultures undergo two 50% fresh FM exchanges, after 3 days in vitro (DIV3), and again at DIV7. Human C-terminal recognition-site Abeta1 Each coated capture-antibody ELISA plate undergoes 4×250 uL/well Phosphate-buffered saline with 0.05% Tween®-20 SigmaUltra (PBS-T; Fluka, cat#79383/Sigma-Aldrich Co., cat#P7949) washes. The ELISA plates are then overlaid with 120 uL/well PBS-T supplemented with 1% Bovine Serum Albumin Diluent/Blocking solution (BSA; Kirkegaard & Perry Laboratories (KPL), Inc., cat#50-61-01) and incubate at room-temperature on an orbital shaker for a minimum of 2 hours. Rat Abeta1 For each ELISA plate, a corresponding transfer-plate is created containing 120 uL/well of either the rat Abeta1 Detection antibody solution is prepared by diluting beta-Amyloid 17-24 (4G8) biotinylated monoclonal antibody (Covance, Inc., cat#SIG-39240-200) 1:1500 in PBS-T supplemented with 0.67% BSA. The ELISA plates undergo 4×250 uL/well PBS-T washes, and are overlaid with 100 uL/well of 4G8 diluted detection-antibody solution. The Abeta1 In order to conjugate the biotinylated monoclonal 4G8 antibody, following 4×250 uL/well PBS-T washes, the ELISA plates undergo a one-hour incubation at 100 ul/well with a 1:15000 dilution of Streptavidin-HRP conjugate (Jackson ImmunoResearch Laboratories, Inc., cat#016-030-0840) on an orbital-shaker at room temperature. Following a final set of 4×250 uL/well PBS-T washes, the ELISA plates are overlaid with 100 ul/well SureBlue 3,3′,5,5′-Tetramethylbenzidine (TMB) Microwell Peroxidase substrate solution (Kirkegaard & Perry Laboratories, Inc., cat#52-00-02), protected from light, and incubate for 20-45 minutes at room temperature. At the point the desired level of development is attained, 100 ul/well of TMB Stop solution (Kirkegaard & Perry Laboratories, Inc., cat#50-85-05) is added, and the plate thoroughly shaken in preparation for reading on a spectrophotometer. SureBlue TMB Microwell Substrate develops a deep blue color in the presence of a peroxidase-labeled conjugate, and turns yellow when stopped by acidification, allowing for plate absorbance at 450 nm to be read. From the calculation of the standard curve, the compound dose-response curves, normalized to DAPT performance, are plotted as % DMSO using GraphPad Prism® software, and the corresponding EC50 values calculated. Compounds of the invention can be used to treat AD in mammal such as a human or alternatively in a validated animal model such as the mouse, rat, or guinea pig. The mammal may not be diagnosed with AD, or may not have a genetic predisposition for AD, but may be transgenic such that it overproduces and eventually deposits Aβ in a manner similar to that seen in the human. Additionally, non-transgenic animals may also be used to determine the biochemical efficacy of the compound, with an appropriate assay. Compounds can be administered in any standard form using any standard method. For example, but not limited to, compounds can be in the form of liquid, tablets or capsules that are taken orally or by injection. Compounds can be administered at any dose that is sufficient to significantly reduce, for example, levels of Aβtotal or more specifically Aβ42 in the blood plasma, cerebrospinal fluid (CSF), or brain. To determine whether acute administration of the compound would reduce Aβ42 levels in-vivo, two-three month old Tg2576 transgenic mice expressing APP695 containing the “Swedish” variant could be used or any other appropriately validated transgenic model. This transgenic mouse displays spontaneous, progressive accumulation of β-amyloid (Aβ) in brain, eventually resulting in amyloid plaques within the subiculum, hippocampus and cortex. Animals of this age have high levels of Aβ in the brain but no detectable Aβ deposition. Mice treated with the compound would be examined and compared to those untreated or treated with vehicle and brain levels of soluble Aβ42 and total Aβ would be quantitated by standard techniques, for example, using ELISA. Treatments may be acute or sub-chronic and treatment periods may vary from hours to days or longer and can be adjusted based on the results of the biochemical endpoint once a time course of onset of effect can be established. A typical protocol for measuring Aβ or Aβ42 levels from in-vivo samples is shown but it is only one of many variations that could used to detect the levels of Aβ. For example, aliquots of compounds can be dissolved in DMSO (volume equal to 1/10th of the final formulation volume), vortexed and further diluted (1:10) with a 10% (w/v) hydroxypropyl β cyclodextrin (HBC, Aldrich, Ref N° 33, 260-7) solution in PBS, where after they are sonicated for 20 seconds.
Blood is collected via cardiac puncture using a 25 gauge needle attached to a 1 ml syringe and was dispensed into a 0.6 ml microtainer tube containing ethylenediaminetetraacetic acid (EDTA). The blood was centrifuged immediately at 4° C. for 5 minutes at 1500×G. The resulting plasma was aliquoted into 0.5 ml microcentrifuge tubes, the aliquots are quick frozen in liquid nitrogen and are stored at −80° C. The brain is removed after removing the skull and is rinsed with PBS. The cerebellum/brain-stem is removed, frozen, and retained for drug exposure analysis; the remaining brain section was quartered. The rear right quarter, which contained cortex and hippocampus, is weighed, frozen in liquid nitrogen and stored at −80° C. until ELISA analysis. The remaining brain tissue is frozen in liquid nitrogen and stored at −80° C. For total Aβ or Aβ40 analysis brain tissue is homogenized at a volume of 24 ml/g in cold 1% CHAPS containing protease inhibitors and the resulting homogenates are centrifuged for 1 hour at 100,000×g at 4° C. The supernatant is removed and transferred to a fresh tube and further diluted to 240 ml/g in CHAPS with protease inhibitors. For Aβ42 analysis brain tissue is homogenized at a volume of 50 ml/g in cold 1% CHAPS containing PI's. Homogenates were spun for 1 hour at 100,000×g at 4° C. The supernatant is removed and transferred to a fresh tube and further to diluted to a final volume 66.7 ml/g in 1% CHAPS with protease inhibitors. To quantify the amount of human Aβ42 in the soluble fraction of the brain homogenates, commercially available Enzyme-Linked-Immunosorbent-Assay (ELISA) kits can be used (h Amyloid Aβ42 ELISA high sensitive, The Genetics Company, Zurich, Switzerland is just one of many examples). The ELISA is performed according to the manufacturer's protocol. Briefly, the standard (a dilution of synthetic Aβ1-42) and samples are prepared in a 96-well polypropylene plate without protein binding capacity (Greiner bio-one, Frickenhausen, Germany). The standard dilutions with final concentrations of 1000, 500, 250, 125, 62.5, 31.3 and 15.6 pg/ml and the samples are prepared in the sample diluent, furnished with the ELISA kit, to a final volume of 60 μl. Samples, standards and blanks (50 μl) are added to the anti-Aβ-coated polystyrol plate (capture antibody selectively recognizes the C-terminal end of the antigen) in addition with a selective anti-Aβ-antibody conjugate (biotinylated detection antibody) and incubated overnight at 4° C. in order to allow formation of the antibody-Amyloid-antibody-complex. The following day, a Streptavidine-Peroxidase-Conjugate is added, followed 30 minutes later by an addition of TMB/peroxide mixture, resulting in the conversion of the substrate into a colored product. This reaction is stopped by the addition of sulfuric acid (1M) and the color intensity is measured by means of photometry with an ELISA-reader with a 450 nm filter. Quantification of the Aβ content of the samples is obtained by comparing absorbance to a standard curve made with synthetic Aβ1-42. Similar analysis, with minor modification, can be carried out with CSF (Diluted 1:10 (for a final loading dilution of 1:100) in 1% CHAPS containing PI and plasma samples (Diluted 1:15 in 0.1% CHAPS [w/v in PBS]). Certain compounds of the disclosure may lower Aβ42 by >15%, in some cases certain compounds may lower Aβ42 >25% and in further cases certain compounds may lower Aβ42 >40% relative to basal levels. Male Sprague Dawley rats from Harlan, 230-350 g, were used for studies. Fasted rats were dosed via oral gavage, with vehicle (15% Solutol HS 15, 10% EtOH, 75% Water) or compound, at a volume of 10 ml/kg. For PK studies, at fixed time points after dosing, the rats were euthanized with an excess of CO2. Terminal blood was collected through cardiac puncture, mixed in EDTA tubes, immediately spun (3 min at 11,000 rpm at 4° C.), and snap frozen for plasma collection. A piece of frontal cortex was collected and snap frozen for compound level determination. For A-beta lowering studies, at a determined time point after dosing (Cmax if it is ≧3 hr), rats were euthanized as in the PK studies and plasma was collected as described above. Cerebellum was removed and saved for compound level determination, and the remaining brain was divided into 4 quadrants, snap frozen and saved to examine A-beta peptide levels. Solutol HS 15 was purchased from Mutchler Inc. Practitioners will also know that similar methods can also be applied to other species such as mice (including transgenic strains such as Tg2576), guinea pig, dog and monkey. Compounds of the invention can be used to treat AD in mammal such as a human or alternatively in a validated animal model such as the mouse, rat, or guinea pig. The mammal may not be diagnosed with AD, or may not have a genetic predisposition for AD, but may be transgenic such that it overproduces and eventually deposits Aβ in a manner similar to that seen in the human. Alternatively, non-transgenic animals may also be used to determine the biochemical efficacy of the compound, that is, the effect on the Aβ biomarker, with an appropriate assay. Compounds can be administered in any standard form using any standard method. For example, but not limited to, compounds can be in the form of liquid, tablets or capsules that are taken orally or by injection. Compounds can be administered at any dose that is sufficient to significantly reduce, for example, levels of Aβtotal or more specifically Aβ42 in the blood plasma, cerebrospinal fluid (CSF), or brain. To determine whether acute administration of the compound would reduce Aβ42 levels in-vivo, two-three month old non-transgenic Sprague-Dawley rats were used. Rats treated with the compound would be examined and compared to those untreated or treated with vehicle and brain levels of soluble Aβ42 and Aβtotal would be quantitated by standard techniques, for example, using an immunoassay such as an ELISA. Treatments may be acute or sub-chronic and treatment periods may vary from hours to days or longer and can be adjusted based on the results of the biochemical endpoint once a time course of onset of effect can be established. A typical protocol for measuring Aβ or Aβ42 levels from in-vivo samples is shown but it is only one of many variations that could used to detect the levels of Aβ.
For total Aβ or Aβ42 analysis brain tissue is homogenized in ten volumes of ice cold 0.4% DEA/50 mM NaCl containing protease inhibitors, e.g., for 0.1 g of brain 1 ml of homogenization buffer is added. Homogenization is achieved either by sonciation for 30 seconds at 3-4 W of power or with a polytron homogenizer at three-quarters speed for 10-15 seconds. Homogenates (1.2 ml) are transferred to pre-chilled centrifuge tubes (Beckman 343778 polycarbonate tubes) are placed into a Beckman TLA120.2 rotor. Homogenates are centrifuged for 1 hour at 100,000 rpm (355,040×g) at 4° C. The resulting supernatants are transferred to fresh sample tubes and placed on ice (the pellets are discarded). The samples are further concentrated and purified by passage over Waters 60 mg HLB Oasis columns according to the methods described (Lanz and Schachter (2006) J. Neurosci Methods. 157(1):71-81; Lanz and Schachter (2008). J. Neurosci Methods. 169(1):16-22). Briefly, using a vacuum manifold (Waters#WAT200607) the columns are attached and conditioned with 1 ml of methanol at a flow rate of 1 ml/minute. Columns are then equilibrated with 1 ml of water. Samples are loaded (800 μl) into individual columns (the Aβ will attach to the column resin). The columns are washed sequentially with 1 ml of 5% methanol followed by 1 ml of 30% methanol. After the final wash the eluates are collected in 13×100 mm tubes by passing 800 μl of solution of 90% methanol/2% ammonium hydroxide) over the columns at 1 ml/minute. The samples are transferred to 1.5 ml non-siliconized sample tubes are dried in a speed-vac concentrator at medium heat for at least 2 hours or until dry. The dried samples are either stored at −80° C. or are used immediately by resuspending the pellets in 80 μl of Ultra-Culture serum-free media (Lonza) supplemented with protease inhibitors by vortexing for 10 seconds. Sixty microliters of each sample is transferred to a pre-coated immunoassay plate coated with an affinity purified rabbit polyclonal antibody specific to Aβ42 (x-42). Sixty microliters of fresh supplemented ultraculture is added to the remaining sample and 60 microliters is transferred to a pre-coated and BSA blocked immunoassay plate coated with an affinity purified rabbit polyclonal antibody specific to total rodent Aβ (1-x). Additional standard samples of rodent Aβ/rodent Aβ42 are also added to the plates with final concentrations of 1000, 500, 250, 125, 62.5, 31.3 and 15.6 pg/ml. The samples are incubated overnight at 4° C. in order to allow formation of the antibody-Amyloid-antibody-complex. The following day the plates are washed 3-4 times with 150 microliters of phosphate buffered saline containing 0.05% Tween 20. After removal of the final wash 100 μl of the monoclonal antibody 4G8 conjugated to biotin (Covance) diluted 1:1000 in PBS-T containing 0.67% BSA was added and the plates incubated at room temperature for 1-2 hours. The plates are again washed 3-4 times with PBS-T and 100 μl of a Streptavidin-Peroxidase-Conjugate diluted 1:10,000 from a 0.5 mg/ml stock in PBS-T contained 0.67% BSA is added and the plates incubated for at least 30 minutes. Following a final set of washes in PBS-T, a TMB/peroxide mixture is added, resulting in the conversion of the substrate into a colored product. This reaction is stopped by the addition of sulfuric acid (1M) and the color intensity is measured by means of photometry with an microplate reader with a 450 nm filter. Quantification of the Aβ content of the samples is obtained by comparing absorbance to a standard curve made with synthetic Aβ. This is one example of a number of possible measureable endpoints for the immunoassay which would give similar results. Plasma samples and standards were prepared for analysis by treating with a 3× volume of acetonitrile containing 500 ng/mL of internal standard (a selected aryl propionic acid). Typically 150 μL of acetonitrile with internal standard was added to 50 μL of plasma. Acetonitrile was added first to each well of a 96-well Phenomenex Strata Impact protein precipitation filter plate followed by the addition of the plasma sample or standard. The filter plate was allowed to sit for at least 15 minutes at room temperature before a vacuum was applied to filter the samples into a clean 96-well plate. If sample concentrations were observed or predicted to be greater than 1000 ng/mL, plasma samples were diluted with blank plasma 10-150 fold depending on the anticipated concentration and upper limit of quantitation of the analytical method. Samples of frontal cortex or cerebellum were homogenized then treated in similar manner. To each brain sample, a 4× volume of PBS (pH 7.4) buffer was added along with a 15× volume of acetonitrile (containing internal standard) in a 2 mL screw-cap plastic tube. The tubes were then filled one third of the way with 1 mm zirconia/silica beads (Biospec) and placed in a Mini Bead Beater for 3 minutes. The samples were inspected and if any visible pieces of brain remained, they were returned to the Bead Beater for another 2-3 minutes of shaking. The resulting suspension was considered to be a 5-fold dilution treated with a 3× volume of acetonitrile (with internal standard). Calibration standards were prepared in 5-fold diluted blank brain homogenate and precipitated with a 3× volume of acetonitrile immediately after the addition of the appropriate spiking solution (see below). All brain standards and samples were allowed to sit for at least 15 minutes prior to filtering them through a Phenomenex Strata Impact protein precipitation filter plate into a clean 96-well plate. Spiking solutions for plasma and brain calibration standards were prepared at concentrations of 0.02, 0.1, 0.2, 1, 2, 10, 20, 100 and 200 μg/mL in 50:50 acetonitrile/water. Calibration standards were prepared by taking 190 μL of blank matrix (plasma or brain homogenate) and adding 10 μL of spiking solution resulting in final concentrations of 1, 5, 10, 50, 100, 500, 1000, 5000 and 10,000 ng/mL. Precipitated plasma and brain samples were analyzed by LC-MS/MS using a Shimadzu LC system consisting of two LC-10AD pumps and a SIL-HTc autosampler connected to an Applied Biosystems MDS/Sciex API 3200 QTRAP mass spectrometer. For chromatographic separation, a Phenomenex Luna C-18 3 μM (2×20 mm) column was used with an acetonitrile-based gradient mobile phase. The two mobile phase components were: Mobile phase A: water with 0.05% (v/v) formic acid and 0.05% (v/v) 5 N ammonium hydroxide. Mobile phase B: 95:5 acetonitrile/water with 0.05% (v/v) formic acid and 0.05% (v/v) 5 N ammonium hydroxide. The gradient for each analysis was optimized for the specific compound, but generally, the run started with between 0% and 40% of mobile phase B, ramped up to 100% of mobile phase B over 1-2 minutes, then held there for 2-3 minutes before returning to the initial conditions for 4 minutes to re-equilibrate. The API 3200 QTRAP mass spectrometer was used in MRM mode with negative electrospray ionization. MRM transitions and mass spec settings were optimized for each compound. Standard curves were created by quadratic or linear regression with 1/x*x weighting. Calibration standards were prepared 1-10,000 ng/mL, but the highest (and sometimes lowest) standards were often not acceptable for quantitation and only those standards with reasonable back-calculated accuracies were included in the calibration curve. Ideally, only standards with +/−15% of nominal concentration would be included in the fitted standard curve, but occasionally larger deviations were accepted after careful consideration. Sample concentrations below the quantitation range were reported as “BQL”. Concentrations above the curve were usually re-run with larger sample dilutions Microsomal glucuronidation reactions were conducted using the UGT Reaction Mix solutions (A and B) from BD Biosciences and following the vendor's protocol. 10 μM of test article or control compound was incubated with 0.5 mg/mL of human or rat liver microsomes. Samples were taken at 0 and 60 minutes and acetonitrile was added to terminate the reactions. Samples were analyzed by LC/MS, monitoring for the loss of parent compound and the appearance of glucuronide. Control reactions were run for each compound substituting water for the glucuronic acid solution to monitor for any loss of parent compound due to degradation or unanticipated microsomal reactions. Hepatocyte experiments were run using cryopreserved human hepatocytes (single donor) obtained from Celsis/In Vitro Technologies. Cells were thawed and counted according to the vendor's protocols using the trypan blue exclusion method to obtain the count of live cells. Test article and control compounds were incubated at a concentration of 5 uM in KHB buffer (Celsis/In Vitro Technologies) containing 1 million cells per mL. Samples were taken at 0, 60 and 120 minutes. The reactions were terminated with addition of acetonitrile. Samples were analyzed by LC/MS, monitoring for the loss of parent compound and the appearance of glucuronide. Compounds of the disclosure are gamma secretase modulators (GSMs), i.e., compounds that act to shift the relative levels of Aβ peptides produced by γ-secretase. In some cases the compounds alter the relative levels of Aβ peptides produced by γ-secretase without significantly changing the total level of Aβ peptides produced. Certain compounds of the disclosure modulate γ-secretase activity with respect to APP proteolytic processing and in so doing lower the production of Aβ42 both in vitro in cells and in vivo in animals. In some cases this effect occurs at concentrations that do not significantly impair the viability of cells in vitro and at doses that are well tolerated in vivo. Certain compounds of the disclosure lower Aβ42 secretion in native neuronal and cellular construct assay systems with EC50 values that are below 1 micromolar (Class A compounds, Table 14) while others have EC50 values from 1-5 micromolar (Class B compounds, Table 14) and others have EC50 values greater than 5 micromolar (Class C compounds). Certain compounds of the disclosure do not appear to significantly interfere with γ-secretase related Notch processing activity. Compounds that significantly interfere with γ-secretase related Notch processing activity have been associated with toxic side-effects. Certain compounds of the disclosure have favorable pharmacokinetic (PK) properties in animals. Thus, certain of the compounds are orally bioavailable, penetrate into the brain and have favorable PK parameters including half-life and clearance supporting pharmaceutical application in humans. In turn, certain compounds of the disclosure significantly lower Aβ42 production in the brains of non-transgenic and transgenic animals after single dose and multi-dose oral administration with no overt side effects. For certain compounds of the disclosure single oral doses of <30 milligrams/kilogram are efficacious at lowering Aβ42 production in the brains of rats (e.g. Sprague-Dawley) and wild type mice (e.g. C57BL/6). Certain compounds of the disclosure which lower Aβ42 at doses of <30 milligrams/kilogram appear to be well tolerated and show no overt or clinical chemical toxicity after subchronic 14-day administration at doses >30 milligrams/kilogram/day. Certain compounds of the disclosure have favorable absorption-distribution-metabolism and excretion (ADME) properties. Moreover, certain compounds of the disclosure do not appear to significantly bio-accumulate in tissues especially in the brain. Compounds of Formulas I-IX wherein A=CO2H show favorable profiles with respect to acylglucoronide (A=CO2Glu) metabolite formation. The potential for acylglucoronide metabolites to cause of toxicity has been described particularly for non-steroidal anti-inflammatory drugs (NSAIDs) containing carboxylic acid groups (Ebner et al Drug Metabolism and Disposition 1999, 27(10), 1143-49). Several such NSAIDs have been removed from the market due to idiosyncratic toxicity in humans and it has been speculated that NSAID idiosyncratic toxicity is related to the relative load and relative reactivity of acylglucoronide metabolites. Therefore, carboxylic acid compounds which are less prone to acylgluconoride formation are expected to be less toxic. As measured using established in vitro assay systems, certain desirable compounds of the disclosure are less prone to acylglucoronidation than NSAID compounds that remain on the market are regarded as safe (e.g., flurbiprofen). The present disclosure includes pharmaceutical composition for treating a subject having a neurological disorder comprising a therapeutically effective amount of a compound of Formulas I-IX, a derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, carrier or diluent. The pharmaceutical compositions can be administered in a variety of dosage forms including, but not limited to, a solid dosage form or in a liquid dosage form, an oral dosage form, a parenteral dosage form, an intranasal dosage form, a suppository, a lozenge, a troche, buccal, a controlled release dosage form, a pulsed release dosage form, an immediate release dosage form, an intravenous solution, a suspension or combinations thereof. The dosage can be an oral dosage form that is a controlled release dosage form. The oral dosage form can be a tablet or a caplet. The compounds can be administered, for example, by oral or parenteral routes, including intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, airway (aerosol), rectal, vaginal and topical (including buccal and sublingual) administration. In one embodiment, the compounds or pharmaceutical compositions comprising the compounds are delivered to a desired site, such as the brain, by continuous injection via a shunt. In another embodiment, the compound can be administered parenterally, such as intravenous (i.v.) administration. The formulations for administration will commonly comprise a solution of the compound of the Formulas I-IX dissolved in a pharmaceutically acceptable carrier. Among the acceptable vehicles and solvents that can be employed are water and Ringer's solution, an isotonic sodium chloride. In addition, sterile fixed oils can conventionally be employed as a solvent or suspending medium. For this purpose any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid can likewise be used in the preparation of injectables. These solutions are sterile and generally free of undesirable matter. These formulations may be sterilized by conventional, well known sterilization techniques. The formulations may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of compound of Formulas I-IX in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight, and the like, in accordance with the particular mode of administration selected and the patient's needs. For i.v. administration, the formulation can be a sterile injectable preparation, such as a sterile injectable aqueous or oleaginous suspension. This suspension can be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a nontoxic parenterally-acceptable diluent or solvent, such as a solution of 1,3-butanediol. In one embodiment, a compound of Formulas I-IX can be administered by introduction into the central nervous system of the subject, e.g., into the cerbrospinal fluid of the subject. The formulations for administration will commonly comprise a solution of the compound of Formulas I-IX dissolved in a pharmaceutically acceptable carrier. In certain aspects, the compound of Formulas I-IX is introduced intrathecally, e.g., into a cerebral ventricle, the lumbar area, or the cisterna magna. In another aspect, the compound of Formulas I-IX is introduced intraocullarly, to thereby contact retinal ganglion cells. The pharmaceutically acceptable formulations can easily be suspended in aqueous vehicles and introduced through conventional hypodermic needles or using infusion pumps. Prior to introduction, the formulations can be sterilized with, preferably, gamma radiation or electron beam sterilization. In one embodiment, the pharmaceutical composition comprising a compound of Formulas I-IX is administered into a subject intrathecally. As used herein, the term “intrathecal administration” is intended to include delivering a pharmaceutical composition comprising a compound of Formulas I-IX directly into the cerebrospinal fluid of a subject, by techniques including lateral cerebroventricular injection through a burrhole or cisternal or lumbar puncture or the like (described in Lazorthes et al. Advances in Drug Delivery Systems and Applications in Neurosurgery, 143-192 and Omaya et al., Cancer Drug Delivery, 1: 169-179, the contents of which are incorporated herein by reference). The term “lumbar region” is intended to include the area between the third and fourth lumbar (lower back) vertebrae. The term “cisterna magna” is intended to include the area where the skull ends and the spinal cord begins at the back of the head. The term “cerebral ventricle” is intended to include the cavities in the brain that are continuous with the central canal of the spinal cord. Administration of a compound of Formulas I-IX to any of the above mentioned sites can be achieved by direct injection of the pharmaceutical composition comprising the compound of Formulas I-IX or by the use of infusion pumps. For injection, the pharmaceutical compositions can be formulated in liquid solutions, preferably in physiologically compatible buffers such as Hank's solution or Ringer's solution. In addition, the pharmaceutical compositions may be formulated in solid form and re-dissolved or suspended immediately prior to use. Lyophilized forms are also included. The injection can be, for example, in the form of a bolus injection or continuous infusion (e.g., using infusion pumps) of pharmaceutical composition. In one embodiment, the pharmaceutical composition comprising a compound of Formulas I-IX is administered by lateral cerebro ventricular injection into the brain of a subject. The injection can be made, for example, through a burr hole made in the subject's skull. In another embodiment, the encapsulated therapeutic agent is administered through a surgically inserted shunt into the cerebral ventricle of a subject. For example, the injection can be made into the lateral ventricles, which are larger, even though injection into the third and fourth smaller ventricles can also be made. In yet another embodiment, the pharmaceutical composition is administered by injection into the cisterna magna, or lumbar area of a subject. For oral administration, the compounds will generally be provided in unit dosage forms of a tablet, pill, dragee, lozenge or capsule; as a powder or granules; or as an aqueous solution, suspension, liquid, gels, syrup, slurry, etc. suitable for ingestion by the patient. Tablets for oral use may include the active ingredients mixed with pharmaceutically acceptable excipients such as inert diluents, disintegrating agents, binding agents, lubricating agents, sweetening agents, flavoring agents, coloring agents and preservatives. Suitable inert diluents include sodium and calcium carbonate, sodium and calcium phosphate, and lactose, while corn starch and alginic acid are suitable disintegrating agents. Binding agents may include starch and gelatin, while the lubricating agent, if present, will generally be magnesium stearate, stearic acid or talc. If desired, the tablets may be coated with a material such as glyceryl monostearate or glyceryl distearate, to delay absorption in the gastrointestinal tract. Pharmaceutical preparations for oral use can be obtained through combination of a compound of Formulas I-IX with a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable additional compounds, if desired, to obtain tablets or dragee cores. Suitable solid excipients in addition to those previously mentioned are carbohydrate or protein fillers that include, but are not limited to, sugars, including lactose, sucrose, mannitol, or sorbitol; starch from corn, wheat, rice, potato, or other plants; cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose or sodium carboxymethylcellulose; and gums including arabic and tragacanth; as well as proteins such as gelatin and collagen. If desired, disintegrating or solubilizing agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, alginic acid, or a salt thereof, such as sodium alginate. Capsules for oral use include hard gelatin capsules in which the active ingredient is mixed with a solid diluent, and soft gelatin capsules wherein the active ingredients is mixed with water or an oil such as peanut oil, liquid paraffin or olive oil. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses. For transmucosal administration (e.g., buccal, rectal, nasal, ocular, etc.), penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art. Formulations for rectal administration may be presented as a suppository with a suitable base comprising for example cocoa butter or a salicylate. Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate. For intramuscular, intraperitoneal, subcutaneous and intravenous use, the compounds will generally be provided in sterile aqueous solutions or suspensions, buffered to an appropriate pH and isotonicity. Suitable aqueous vehicles include Ringer's solution and isotonic sodium chloride. Aqueous suspensions may include suspending agents such as cellulose derivatives, sodium alginate, polyvinyl-pyrrolidone and gum tragacanth, and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n-propyl p-hydroxybenzoate. The suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient which is solid at ordinary temperatures but liquid at the rectal temperatures and will therefore melt in the rectum to release the drug. Such materials are cocoa butter and polyethylene glycols. The compounds can be delivered transdermally, by a topical route, formulated as applicator sticks, solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, or aerosols. The compounds may also be presented as aqueous or liposome formulations. Aqueous suspensions can contain a compound of Formulas I-IX in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include a suspending agent, such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth and gum acacia, and dispersing or wetting agents such as a naturally occurring phosphatide (e.g., lecithin), a condensation product of an alkylene oxide with a fatty acid (e.g., polyoxyethylene stearate), a condensation product of ethylene oxide with a long chain aliphatic alcohol (e.g., heptadecaethylene oxycetanol), a condensation product of ethylene oxide with a partial ester derived from a fatty acid and a hexitol (e.g., polyoxyethylene sorbitol mono-oleate), or a condensation product of ethylene oxide with a partial ester derived from fatty acid and a hexitol anhydride (e.g., polyoxyethylene sorbitan monooleate). The aqueous suspension can also contain one or more preservatives such as ethyl or n-propyl p-hydroxybenzoate, one or more coloring agents, one or more flavoring agents and one or more sweetening agents, such as sucrose, aspartame or saccharin. Formulations can be adjusted for osmolarity. Oil suspensions can be formulated by suspending a compound of Formulas I-IX in a vegetable oil, such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin; or a mixture of these. The oil suspensions can contain a thickening agent, such as beeswax, hard paraffin or cetyl alcohol. Sweetening agents can be added to provide a palatable oral preparation, such as glycerol, sorbitol or sucrose. These formulations can be preserved by the addition of an antioxidant such as ascorbic acid. As an example of an injectable oil vehicle, see Minto, J. Pharmacol. Exp. Ther. 281:93-102, 1997. The pharmaceutical formulations can also be in the form of oil-in-water emulsions. The oily phase can be a vegetable oil or a mineral oil, described above, or a mixture of these. Suitable emulsifying agents include naturally-occurring gums, such as gum acacia and gum tragacanth, naturally occurring phosphatides, such as soybean lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan mono-oleate, and condensation products of these partial esters with ethylene oxide, such as polyoxyethylene sorbitan mono-oleate. The emulsion can also contain sweetening agents and flavoring agents, as in the formulation of syrups and elixirs. Such formulations can also contain a demulcent, a preservative, or a coloring agent. In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation or transcutaneous delivery (e.g., subcutaneously or intramuscularly), intramuscular injection or a transdermal patch. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt. The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients. Examples of such carriers or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. For administration by inhalation, the compounds are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. In general a suitable dose will be in the range of 0.01 to 100 mg per kilogram body weight of the recipient per day, preferably in the range of 0.2 to 10 mg per kilogram body weight per day. The desired dose is preferably presented once daily, but may be dosed as two, three, four, five, six or more sub-doses administered at appropriate intervals throughout the day. The compounds can be administered as the sole active agent, or in combination with other known therapeutics to be beneficial in the treatment of neurological disorders. In any event, the administering physician can provide a method of treatment that is prophylactic or therapeutic by adjusting the amount and timing of drug administration on the basis of observations of one or more symptoms (e.g., motor or cognitive function as measured by standard clinical scales or assessments) of the disorder being treated. Details on techniques for formulation and administration are well described in the scientific and patent literature, see, e.g., the latest edition of Remington's Pharmaceutical Sciences, Maack Publishing Co, Easton Pa. (“Remington's After a pharmaceutical composition has been formulated in an acceptable carrier, it can be placed in an appropriate container and labeled for treatment of an indicated condition. For administration of the compounds of Formulas I-IX, such labeling would include, e.g., instructions concerning the amount, frequency and method of administration. Tetrasubstituted benzenes that act as modulators of gamma secretase and their use in the treatment of one or more symptoms of treating neurodegenerative disorders, e.g., Alzheimer's disease, are described. 1.-62. (canceled) 63. A compound of Formula III or a pharmaceutically acceptable salt thereof, wherein:
R1 and R2 are independently selected from the group consisting of (a) H, (b) F, (c) OH, (d) OR6, (e) SR6, (f) (C2-C6)alkyl, (g) a C1-C6 alkyl that is independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (h) (C0-C3)alkyl-(C3-C7)cycloalkyl, (i) heterocycloalkylalkyl and (j) (CH2)nQ wherein n=0-2 and wherein Q is a monocyclic or bicyclic aromatic or heteroaromatic ring system having 5 to 10 ring atoms independently selected from the group consisting of C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, and wherein Q is optionally independently substituted with up to 3 groups selected from the group consisting of alkyl, halogen, CF3, OH, OCF3, alkoxy, OCH2CH2OCH3, NH2, alkylamino, dialkylamino, morpholino, CN, NO2, alkylthio and alkylsulfonyl, provided that both R1 and R2 are not H, wherein each alkyl or cycloalkyl of R1 and R2 is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CF3 and C1-C4 alkyl, or R1 and R2 taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl or heterocycloalkyl ring which optionally bears a C1-C4 alkyl substituent that can be optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, oxo, cyano, CF3 and C1-C4 alkyl; or R1 and R2 are taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring substituted with R20 and R21 wherein R20 and R21 taken together with the carbon or carbons to which they are attached form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CF3 and C1-C4 alkyl; R6 is selected from the group consisting of
(a) C1-C6 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (b) (C0-C3)alkyl-(C3-C7)cycloalkyl, (c) heterocycloalkylalkyl and (d) (CH2)nQ wherein n=0-2 and wherein Q is a monocyclic or bicyclic aromatic or heteroaromatic ring system having 5 to 10 ring atoms independently selected from the group consisting of C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, and wherein Q is optionally independently substituted with up to 3 groups selected from the group consisting of alkyl, halogen, CF3, OH, OCF3, alkoxy, OCH2CH2OCH3, NH2, alkylamino, dialkylamino, morpholino, CN, NO2, alkylthio and alkylsulfonyl; each R7 is independently selected from the group consisting of C1-C6 alkyl, alkoxyethyl, (C3-C7)cycloalkyl, (C0-C3)alkyl-(C3-C7)cycloalkyl and heterocycloalkylalkyl; Y is —O—; R4 is selected from the group consisting of
(a) C1-C7 alkyl group optionally and independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (b) (C0-C3)alkyl-(C3-C7)cycloalkyl, (c) heterocycloalkylalkyl, (d) trifluoroethyl and (e) trifluoropropyl; Z is aryl or heteroaryl having 5 to 10 ring atoms independently selected from the group consisting of C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, said ring system optionally bearing up to 3 substituents independently selected from the group consisting of halogen, R6, CF3, CN, NO2, OH, (C1-C4)alkoxy, aryloxy, heteroaryloxy, OCH2CH2OCH3, OC(O)R6, OC(O)OR6, OC(O)NHR7, OC(O)N(R7)2, SR6, S(O)R6, S(O)2R6, S(O)2NHR7, S(O)2N(R7)2, NHR7, N(R7)2, NHC(O)R6, N(R7)C(O)R6, NHC(O)OR6, N(R7)C(O)OR6, N(R7)C(O)NH(R7), N(R7)C(O)NH(R7)2, C(O)NH2, C(O)NHR7, C(O)N(R7)2, CO2H, CO2R6 and COR6; and R5 is selected from the group consisting of NO2, NH2, CF3, F, Cl, Br, SR6, S(O)2R6, S(O)2N(R7)2 and (C1-C4)alkoxy substituted with halo or CF3. 64. The compound of or R1 and R2 taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl or heterocycloalkyl ring which optionally bears a C1-C4 alkyl substituent that can be optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, oxo, cyano, CF3 and (C1-C4)alkyl, or R1 and R2 are taken together with the carbon to which they are attached form a 3-7 membered cycloalkyl ring substituted with R20 and R21 wherein R20 and R21 taken together with the carbon or carbons to which they are attached form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently substituted with one or more groups selected from the group consisting of halo, hydroxy, cyano, CF3 and (C1-C4)alkyl; Y is —O—, R4 is selected from the group consisting of
(a) (C0-C3)alkyl(C3-C7)cycloalkyl, (b) trifluoroethyl and (c) trifluoropropyl; Z is a phenyl ring optionally bearing up to 3 substituents independently selected from the group consisting of halogen, R6, CF3, CN, NO2, OH, (C1-C4)alkoxy, OCH2CH2OCH3, SR6, S(O)R6 and S(O)2R6; R5 is selected from the group consisting of CF3, F, Cl and Br; and
R6 is selected from the group consisting of (a) (C1-C6)alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O), or —S(O)2— groups; (b) (C0-C3)alkyl(C3-C7)cycloalkyl and (c) heterocycloalkylalkyl; or a pharmaceutically acceptable salt thereof. 65. The compound of 66. The compound of 67. The compound of 68. The compound of 69. The compound of 70. The compound of provided that both R1 and R2 are not H; or a pharmaceutically acceptable salt thereof. 71. The compound of 72. The compound of 73. The compound of 74. The compound of 75. The compound of 76. The compound of 77. The compound of (a) C1-C6 alkyl, (b) (C0-C3)alkyl-(C3-C7)cycloalkyl and (c) heterocycloalkylalkyl; or a pharmaceutically acceptable salt thereof. 78. The compound of (a) (C1-C7)alkyl, (b) (C0-C3)alkyl-(C3-C7)cycloalkyl, (c) heterocycloalkylalkyl, (d) trifluoroethyl, and (e) trifluoropropyl; or a pharmaceutically acceptable salt thereof. 79. The compound of 80. The compound of 81. The compound of 82. The compound of 83. The compound of 84. The compound of 85. The compound of 86. The compound of 87. The compound of 88. The compound of 89. The compound of 90. The compound of 91. The compound of 92. A compound selected from the group consisting of examples 100-389, 400-413, 416-559, 980-982, 985-1267, 1269-1271, 1273-1299, 1303-1307, 1309-1311, 1315-1319, 1321-1529, 1529a, 1530-1540, 2704-2718, 2721-2754 and 2757-2859 or a pharmaceutically acceptable salt thereof. 93. A pharmaceutical composition comprising the compound of any one of 94. A method for the therapeutic treatment of a neurodegenerative disorder or improving cognition comprising administering to a patient in need thereof an effective amount of the compound of 95. The method of RELATED APPLICATION INFORMATION
BACKGROUND
SUMMARY
Wherein:
R1 and R2 are independently selected from: (a) H, (b) F, (c) OH, (d) OR6, (e) SR6, (f) NHR7, (g) N(R7)2 (h) NHC(O)R6, (i) NHCO2R6, (j) (C2-C6)alkyl, (k) (C0-C3)alkyl-(C3-C7)cycloalkyl, (l) C1-C6 alkyl that is independently interrupted by one or more —O—, —S—, —S(O)—, or —S(O)2— groups, (m) (C3-C7)cycloalkyl, (n) (C0-C3)alkyl-(C3-C7)cycloalkyl, (o) heterocycloalkylalky and (p) (CH2)nQ wherein n=0-2 and wherein Q is a mono- or bicyclic aromatic or heteroaromatic ring system having 5 to 10 ring atoms independently selected from C, N, O and S, provided that not more than 3 ring atoms in any single ring are other than C, and wherein Q is optionally independently substituted with up to 3 groups selected from alkyl, halogen, CF3, OH, OCF3, alkoxy, OCH2CH2OCH3, NH2, alkylamino, dialkylamino, morpholino, CN, NO2, alkylthio and alkylsulfonyl,
R1 and R2 are taken together to form a 3-7 membered cycloalkyl or heterocycloalkyl ring which is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl,
or
R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring substituted with R20 and R21 where R20 and R21 are taken together to form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl
R6 is selected from:
X is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7)—, —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S—, —CH2SCH2—, —C(O)NH—, —C(O)N(R7)—, —NHC(O)—, —N(R7)C(O)—, —S(O)—, —S(O2)—, —S(O)2N(H)—, —S(O)2N(R7)—, —N(H)S(O)2—, —N(R7)S(O)2— wherein the point of attachment of divalent linking groups, X, to R3 in the Formulas I and II is to the right;
Y is a bond or a divalent linking group selected from —O—, —OCH2—, —OCH(R7), —OCH2CH2—, —CH2—, —C(O)—, —CH═CH—, —CH2CH2—, —CH2O—, —CH2OCH2—, —CH2CH2O—, —S—, —SCH2—, CH2S—, —CH2SCH2—, —C(O)NH—, —C(O)N(R7)—, —NHC(O)—, —N(R7)C(O)—, —S(O)—, —S(O2)—, —S(O)2N(H)—, —S(O)2N(R7)—, —N(H)S(O)2—, —N(R7)S(O)2— wherein the point of attachment of divalent linking groups, Y, to R4 in the Formulas I and II is to the right;
R3 is (a) C1-C7 alkyl optionally and independently interrupted by one or more —O—, —S—, —S(O)—, and —S(O)2— groups,
provided that one or both of R3 and R4 is Z.
R1 and R2 are taken together to form a 3-7 membered cycloalkyl or heterocycloalkyl ring which are; optionally independently singly or multiply substituted with halo, hydroxy, cyano, CF3, C1-C4 alkyl
or
R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring substituted with R20 and R21 where R20 and R21 are taken together to form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl.
R1 and R2 are taken together to form a 3-7 membered cycloalkyl ring substituted with R20 and R21 where R20 and R21 are taken together to form a 3-7 membered cycloalkyl ring wherein each cycloalkyl is optionally independently singly or multiply substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl.
In another embodiment R1 and R2 if not H are optionally singly or multiply independently substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl
In another embodiment R1 and R2 if not H are singly or multiply independently substituted with halo, hydroxy, oxo, cyano, CF3, C1-C4 alkyl
In another embodiment a single enantiomer of the previous embodiments is selected.
In another embodiment a single enantiomer of configuration (R) of the previous embodiments is selected.
In another embodiment a single enantiomer of configuration (S) of the previous embodiments is selected.
In another embodiment a solvate of a compound of formula (I-IX) is selected.
In another embodiment a polymorph of compound of formula (I-IX) is selected.
In a separate embodiment, a pharmaceutical composition comprising of the compound of the previous embodiments and a pharmaceutically acceptable carrier.
DESCRIPTION OF THE FIGURE
DETAILED DESCRIPTION
General Reaction Schemes
Enantioselective Methods
Formula III Ex R1 R2 Y R4 R5 Z 100 CH3 H O CH2CH3 F 4-fluorophenyl 101 CH2CH3 H O CH2CH3 F 4-fluorophenyl 102 CH2CF3 H O CH2CH3 F 4-fluorophenyl 103 CH2CH2CH3 H O CH2CH3 F 4-fluorophenyl 104 CH2CH(CH3)2 H O CH2CH3 F 4-fluorophenyl 105 cyclopropylmethyl H O CH2CH3 F 4-fluorophenyl 106 SCH(CH3)2 H O CH2CH3 F 4-fluorophenyl 107 OCH2CH3 H O CH2CH3 F 4-fluorophenyl 108 (CH2)2 O CH2CH3 F 4-fluorophenyl 109 (CH2)4 O CH2CH3 F 4-fluorophenyl 110 CH3 H O CH2CH3 F 4-chlorophenyl 111 CH2CH3 H O CH2CH3 F 4-chlorophenyl 112 CH2CF3 H O CH2CH3 F 4-chlorophenyl 113 CH2CH2CH3 H O CH2CH3 F 4-chlorophenyl 114 CH2CH(CH3)2 H O CH2CH3 F 4-chlorophenyl 115 cyclopropylmethyl H O CH2CH3 F 4-chlorophenyl 116 SCH(CH3)2 H O CH2CH3 F 4-chlorophenyl 117 OCH2CH3 H O CH2CH3 F 4-chlorophenyl 118 (CH2)2 O CH2CH3 F 4-chlorophenyl 119 (CH2)4 O CH2CH3 F 4-chlorophenyl 120 CH3 H O CH2CH3 F 4-trifluoromethylphenyl 121 CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 122 CH2CF3 H O CH2CH3 F 4-trifluoromethylphenyl 123 CH2CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 124 CH2CH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 125 cyclopropylmethyl H O CH2CH3 F 4-trifluoromethylphenyl 126 SCH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 127 OCH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 128 (CH2)2 O CH2CH3 F 4-trifluoromethylphenyl 129 (CH2)4 O CH2CH3 F 4-trifluoromethylphenyl 130 CH3 H O CH2CH3 F 4-methoxyphenyl 131 CH2CH3 H O CH2CH3 F 4-methoxyphenyl 132 CH2CF3 H O CH2CH3 F 4-methoxyphenyl 133 CH2CH2CH3 H O CH2CH3 F 4-methoxyphenyl 134 CH2CH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 135 cyclopropylmethyl H O CH2CH3 F 4-methoxyphenyl 136 SCH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 137 OCH2CH3 H O CH2CH3 F 4-methoxyphenyl 138 (CH2)2 O CH2CH3 F 4-methoxyphenyl 139 (CH2)4 O CH2CH3 F 4-methoxyphenyl 140 CH3 H O CH2CH3 F 3,4 dichloro phenyl 141 CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 142 CH2CF3 H O CH2CH3 F 3,4 dichloro phenyl 143 CH2CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 144 CH2CH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 145 cyclopropylmethyl H O CH2CH3 F 3,4 dichloro phenyl 146 SCH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 147 OCH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 148 (CH2)2 O CH2CH3 F 3,4 dichloro phenyl 149 (CH2)4 O CH2CH3 F 3,4 dichloro phenyl 150 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 151 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 152 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 153 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 154 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 155 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 156 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 157 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 158 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 159 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 160 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 161 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 162 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 163 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 164 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 165 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 166 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 167 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 168 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 169 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 170 CH3 H O CH2CF3 F 4-fluorophenyl 171 CH2CH3 H O CH2CF3 F 4-fluorophenyl 172 CH2CF3 H O CH2CF3 F 4-fluorophenyl 173 CH2CH2CH3 H O CH2CF3 F 4-fluorophenyl 174 CH2CH(CH3)2 H O CH2CF3 F 4-fluorophenyl 175 cyclopropylmethyl H O CH2CF3 F 4-fluorophenyl 176 SCH(CH3)2 H O CH2CF3 F 4-fluorophenyl 177 OCH2CH3 H O CH2CF3 F 4-fluorophenyl 178 (CH2)2 O CH2CF3 F 4-fluorophenyl 179 (CH2)4 O CH2CF3 F 4-fluorophenyl 180 CH3 H O CH2CF3 F 4-chlorophenyl 181 CH2CH3 H O CH2CF3 F 4-chlorophenyl 182 CH2CF3 H O CH2CF3 F 4-chlorophenyl 183 CH2CH2CH3 H O CH2CF3 F 4-chlorophenyl 184 CH2CH(CH3)2 H O CH2CF3 F 4-chlorophenyl 185 cyclopropylmethyl H O CH2CF3 F 4-chlorophenyl 186 SCH(CH3)2 H O CH2CF3 F 4-chlorophenyl 187 OCH2CH3 H O CH2CF3 F 4-chlorophenyl 188 (CH2)2 O CH2CF3 F 4-chlorophenyl 189 (CH2)4 O CH2CF3 F 4-chlorophenyl 190 CH3 H O CH2CF3 F 4-trifluoromethylphenyl 191 CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 192 CH2CF3 H O CH2CF3 F 4-trifluoromethylphenyl 193 CH2CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 194 CH2CH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 195 cyclopropylmethyl H O CH2CF3 F 4-trifluoromethylphenyl 196 SCH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 197 OCH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 198 (CH2)2 O CH2CF3 F 4-trifluoromethylphenyl 199 (CH2)4 O CH2CF3 F 4-trifluoromethylphenyl 200 CH3 H O CH2CF3 F 4-methoxyphenyl 201 CH2CH3 H O CH2CF3 F 4-methoxyphenyl 202 CH2CF3 H O CH2CF3 F 4-methoxyphenyl 203 CH2CH2CH3 H O CH2CF3 F 4-methoxyphenyl 204 CH2CH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 205 cyclopropylmethyl H O CH2CF3 F 4-methoxyphenyl 206 SCH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 207 OCH2CH3 H O CH2CF3 F 4-methoxyphenyl 208 (CH2)2 O CH2CF3 F 4-methoxyphenyl 209 (CH2)4 O CH2CF3 F 4-methoxyphenyl 210 CH3 H O CH2CF3 F 3,4 dichloro phenyl 211 CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 212 CH2CF3 H O CH2CF3 F 3,4 dichloro phenyl 213 CH2CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 214 CH2CH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 215 cyclopropylmethyl H O CH2CF3 F 3,4 dichloro phenyl 216 SCH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 217 OCH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 218 (CH2)2 O CH2CF3 F 3,4 dichloro phenyl 219 (CH2)4 O CH2CF3 F 3,4 dichloro phenyl 220 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 221 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 222 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 223 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 224 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 225 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 226 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 227 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 228 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 229 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 230 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 231 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 232 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 233 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 234 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 235 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 236 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 237 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 238 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 239 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 240 CH3 H O CH2—c-Pr F 4-fluorophenyl 241 CH2CH3 H O CH2—c-Pr F 4-fluorophenyl 242 CH2CF3 H O CH2—c-Pr F 4-fluorophenyl 243 CH2CH2CH3 H O CH2—c-Pr F 4-fluorophenyl 244 CH2CH(CH3)2 H O CH2—c-Pr F 4-fluorophenyl 245 cyclopropylmethyl H O CH2—c-Pr F 4-fluorophenyl 246 SCH(CH3)2 H O CH2—c-Pr F 4-fluorophenyl 247 OCH2CH3 H O CH2—c-Pr F 4-fluorophenyl 248 (CH2)2 O CH2—c-Pr F 4-fluorophenyl 249 (CH2)4 O CH2—c-Pr F 4-fluorophenyl 250 CH3 H O CH2—c-Pr F 4-chlorophenyl 251 CH2CH3 H O CH2—c-Pr F 4-chlorophenyl 252 CH2CF3 H O CH2—c-Pr F 4-chlorophenyl 253 CH2CH2CH3 H O CH2—c-Pr F 4-chlorophenyl 254 CH2CH(CH3)2 H O CH2—c-Pr F 4-chlorophenyl 255 cyclopropylmethyl H O CH2—c-Pr F 4-chlorophenyl 256 SCH(CH3)2 H O CH2—c-Pr F 4-chlorophenyl 257 OCH2CH3 H O CH2—c-Pr F 4-chlorophenyl 258 (CH2)2 O CH2—c-Pr F 4-chlorophenyl 259 (CH2)4 O CH2—c-Pr F 4-chlorophenyl 260 CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 261 CH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 262 CH2CF3 H O CH2—c-Pr F 4-trifluoromethylphenyl 263 CH2CH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 264 CH2CH(CH3)2 H O CH2—c-Pr F 4-trifluoromethylphenyl 265 cyclopropylmethyl H O CH2—c-Pr F 4-trifluoromethylphenyl 266 SCH(CH3)2 H O CH2—c-Pr F 4-trifluoromethylphenyl 267 OCH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 268 (CH2)2 O CH2—c-Pr F 4-trifluoromethylphenyl 269 (CH2)4 O CH2—c-Pr F 4-trifluoromethylphenyl 270 CH3 H O CH2—c-Pr F 4-methoxyphenyl 271 CH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 272 CH2CF3 H O CH2—c-Pr F 4-methoxyphenyl 273 CH2CH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 274 CH2CH(CH3)2 H O CH2—c-Pr F 4-methoxyphenyl 275 cyclopropylmethyl H O CH2—c-Pr F 4-methoxyphenyl 276 SCH(CH3)2 H O CH2—c-Pr F 4-methoxyphenyl 277 OCH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 278 (CH2)2 O CH2—c-Pr F 4-methoxyphenyl 279 (CH2)4 O CH2—c-Pr F 4-methoxyphenyl 280 CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 281 CH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 282 CH2CF3 H O CH2—c-Pr F 3,4 dichloro phenyl 283 CH2CH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 284 CH2CH(CH3)2 H O CH2—c-Pr F 3,4 dichloro phenyl 285 cyclopropylmethyl H O CH2—c-Pr F 3,4 dichloro phenyl 286 SCH(CH3)2 H O CH2—c-Pr F 3,4 dichloro phenyl 287 OCH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 288 (CH2)2 O CH2—c-Pr F 3,4 dichloro phenyl 289 (CH2)4 O CH2—c-Pr F 3,4 dichloro phenyl 290 CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 291 CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 292 CH2CF3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 293 CH2CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 294 CH2CH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 295 cyclopropylmethyl H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 296 SCH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 297 OCH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 298 (CH2)2 O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 299 (CH2)4 O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 300 CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 301 CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 302 CH2CF3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 303 CH2CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 304 CH2CH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 305 cyclopropylmethyl H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 306 SCH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 307 OCH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 308 (CH2)2 O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 309 (CH2)4 O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 310 CH3 H O CH2CH3 Cl 4-fluorophenyl 311 CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 312 CH2CF3 H O CH2CH3 Cl 4-fluorophenyl 313 CH2CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 314 CH2CH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 315 cyclopropylmethyl H O CH2CH3 Cl 4-fluorophenyl 316 SCH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 317 OCH2CH3 H O CH2CH3 Cl 4-fluorophenyl 318 (CH2)2 O CH2CH3 Cl 4-fluorophenyl 319 (CH2)4 O CH2CH3 Cl 4-fluorophenyl 320 CH3 H O CH2CH3 Cl 4-chlorophenyl 321 CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 322 CH2CF3 H O CH2CH3 Cl 4-chlorophenyl 323 CH2CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 324 CH2CH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 325 cyclopropylmethyl H O CH2CH3 Cl 4-chlorophenyl 326 SCH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 327 OCH2CH3 H O CH2CH3 Cl 4-chlorophenyl 328 (CH2)2 O CH2CH3 Cl 4-chlorophenyl 329 (CH2)4 O CH2CH3 Cl 4-chlorophenyl 330 CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 331 CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 332 CH2CF3 H O CH2CH3 Cl 4-trifluoromethylphenyl 333 CH2CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 334 CH2CH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 335 cyclopropylmethyl H O CH2CH3 Cl 4-trifluoromethylphenyl 336 SCH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 337 OCH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 338 (CH2)2 O CH2CH3 Cl 4-trifluoromethylphenyl 339 (CH2)4 O CH2CH3 Cl 4-trifluoromethylphenyl 340 CH3 H O CH2CH3 Cl 4-methoxyphenyl 341 CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 342 CH2CF3 H O CH2CH3 Cl 4-methoxyphenyl 343 CH2CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 344 CH2CH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 345 cyclopropylmethyl H O CH2CH3 Cl 4-methoxyphenyl 346 SCH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 347 OCH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 348 (CH2)2 O CH2CH3 Cl 4-methoxyphenyl 349 (CH2)4 O CH2CH3 Cl 4-methoxyphenyl 350 CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 351 CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 352 CH2CF3 H O CH2CH3 Cl 3,4 dichloro phenyl 353 CH2CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 354 CH2CH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 355 cyclopropylmethyl H O CH2CH3 Cl 3,4 dichloro phenyl 356 SCH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 357 OCH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 358 (CH2)2 O CH2CH3 Cl 3,4 dichloro phenyl 359 (CH2)4 O CH2CH3 Cl 3,4 dichloro phenyl 360 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 361 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 362 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 363 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 364 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 365 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 366 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 367 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 368 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 369 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 370 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 371 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 372 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 373 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 374 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 375 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 376 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 377 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 378 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 379 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 380 CH3 H O CH2CF3 Cl 4-fluorophenyl 381 CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 382 CH2CF3 H O CH2CF3 Cl 4-fluorophenyl 383 CH2CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 384 CH2CH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 385 cyclopropylmethyl H O CH2CF3 Cl 4-fluorophenyl 386 SCH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 387 OCH2CH3 H O CH2CF3 Cl 4-fluorophenyl 388 (CH2)2 O O CH2CF3 Cl 4-fluorophenyl 389 (CH2)4 O O CH2CF3 Cl 4-fluorophenyl 400 CH3 H O CH2CF3 Cl 4-chlorophenyl 401 CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 402 CH2CF3 H O CH2CF3 Cl 4-chlorophenyl 403 CH2CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 404 CH2CH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 405 cyclopropylmethyl H O CH2CF3 Cl 4-chlorophenyl 406 SCH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 407 OCH2CH3 H O CH2CF3 Cl 4-chlorophenyl 408 (CH2)2 O CH2CF3 Cl 4-chlorophenyl 409 (CH2)4 O CH2CF3 Cl 4-chlorophenyl 410 CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 411 CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 412 CH2CF3 H O CH2CF3 Cl 4-trifluoromethylphenyl 413 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 414 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 415 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethylphenyl 416 SCH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 417 OCH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 418 (CH2)2 O CH2CF3 Cl 4-trifluoromethylphenyl 419 (CH2)4 O CH2CF3 Cl 4-trifluoromethylphenyl 420 CH3 H O CH2CF3 Cl 4-methoxyphenyl 421 CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 422 CH2CF3 H O CH2CF3 Cl 4-methoxyphenyl 423 CH2CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 424 CH2CH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 425 cyclopropylmethyl H O CH2CF3 Cl 4-methoxyphenyl 426 SCH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 427 OCH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 428 (CH2)2 O CH2CF3 Cl 4-methoxyphenyl 429 (CH2)4 O CH2CF3 Cl 4-methoxyphenyl 430 CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 431 CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 432 CH2CF3 H O CH2CF3 Cl 3,4 dichloro phenyl 433 CH2CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 434 CH2CH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 435 cyclopropylmethyl H O CH2CF3 Cl 3,4 dichloro phenyl 436 SCH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 437 OCH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 438 (CH2)2 O CH2CF3 Cl 3,4 dichloro phenyl 439 (CH2)4 O CH2CF3 Cl 3,4 dichloro phenyl 440 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 441 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 442 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 443 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 444 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 445 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 446 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 447 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 448 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 449 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 450 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 451 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 452 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 453 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 454 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 455 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 456 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 457 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 458 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 459 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 460 CH3 H O CH2—c-Pr Cl 4-fluorophenyl 461 CH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 462 CH2CF3 H O CH2—c-Pr Cl 4-fluorophenyl 463 CH2CH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 464 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-fluorophenyl 465 cyclopropylmethyl H O CH2—c-Pr Cl 4-fluorophenyl 466 SCH(CH3)2 H O CH2—c-Pr Cl 4-fluorophenyl 467 OCH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 468 (CH2)2 O CH2—c-Pr Cl 4-fluorophenyl 469 (CH2)4 O CH2—c-Pr Cl 4-fluorophenyl 470 CH3 H O CH2—c-Pr Cl 4-chlorophenyl 471 CH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 472 CH2CF3 H O CH2—c-Pr Cl 4-chlorophenyl 473 CH2CH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 474 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-chlorophenyl 475 cyclopropylmethyl H O CH2—c-Pr Cl 4-chlorophenyl 476 SCH(CH3)2 H O CH2—c-Pr Cl 4-chlorophenyl 477 OCH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 478 (CH2)2 O CH2—c-Pr Cl 4-chlorophenyl 479 (CH2)4 O CH2—c-Pr Cl 4-chlorophenyl 480 CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 481 CH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 482 CH2CF3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 483 CH2CH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 484 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 485 cyclopropylmethyl H O CH2—c-Pr Cl 4-trifluoromethylphenyl 486 SCH(CH3)2 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 487 OCH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 488 (CH2)2 O CH2—c-Pr Cl 4-trifluoromethylphenyl 489 (CH2)4 O CH2—c-Pr Cl 4-trifluoromethylphenyl 490 CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 491 CH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 492 CH2CF3 H O CH2—c-Pr Cl 4-methoxyphenyl 493 CH2CH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 494 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-methoxyphenyl 495 cyclopropylmethyl H O CH2—c-Pr Cl 4-methoxyphenyl 496 SCH(CH3)2 H O CH2—c-Pr Cl 4-methoxyphenyl 497 OCH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 498 (CH2)2 O CH2—c-Pr Cl 4-methoxyphenyl 499 (CH2)4 O CH2—c-Pr Cl 4-methoxyphenyl 500 CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 501 CH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 502 CH2CF3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 503 CH2CH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 504 CH2CH(CH3)2 H O CH2—c-Pr Cl 3,4 dichloro phenyl 505 cyclopropylmethyl H O CH2—c-Pr Cl 3,4 dichloro phenyl 506 SCH(CH3)2 H O CH2—c-Pr Cl 3,4 dichloro phenyl 507 OCH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 508 (CH2)2 O CH2—c-Pr Cl 3,4 dichloro phenyl 509 (CH2)4 O CH2—c-Pr Cl 3,4 dichloro phenyl 510 CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 511 CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 512 CH2CF3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 513 CH2CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 514 CH2CH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 515 cyclopropylmethyl H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 516 SCH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 517 OCH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 518 (CH2)2 O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 519 (CH2)4 O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 520 CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 521 CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 522 CH2CF3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 523 CH2CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 524 CH2CH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 525 cyclopropylmethyl H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 526 SCH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 527 OCH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 528 (CH2)2 O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 529 (CH2)4 O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 530 CH3 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 531 CH2CH3 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 532 CH2CF3 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 533 CH2CH2CH3 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 534 CH2CH(CH3)2 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 535 cyclopropylmethyl H O CH2—c-Pr NO2 4-trifluoromethylphenyl 536 SCH(CH3)2 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 537 OCH2CH3 H O CH2—c-Pr NO2 4-trifluoromethylphenyl 538 (CH2)2 O CH2—c-Pr NO2 4-trifluoromethylphenyl 539 (CH2)4 O CH2—c-Pr NO2 4-trifluoromethylphenyl 540 CH3 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 541 CH2CH3 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 542 CH2CF3 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 543 CH2CH2CH3 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 544 CH2CH(CH3)2 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 545 cyclopropylmethyl H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 546 SCH(CH3)2 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 547 OCH2CH3 H O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 548 (CH2)2 O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 549 (CH2)4 O CH2—c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 550 CH3 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 551 CH2CH3 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 552 CH2CF3 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 553 CH2CH2CH3 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 554 CH2CH(CH3)2 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 555 cyclopropylmethyl H O CH2—c-Pr NH2 4-trifluoromethylphenyl 556 SCH(CH3)2 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 557 OCH2CH3 H O CH2—c-Pr NH2 4-trifluoromethylphenyl 558 (CH2)2 O CH2—c-Pr NH2 4-trifluoromethylphenyl 559 (CH2)4 O CH2—c-Pr NH2 4-trifluoromethylphenyl Formula V EX R1 R2 X R3 R5 Z 560 CH3 H O CH2CH3 F 4-fluorophenyl 561 CH2CH3 H O CH2CH3 F 4-fluorophenyl 562 CH2CF3 H O CH2CH3 F 4-fluorophenyl 563 CH2CH2CH3 H O CH2CH3 F 4-fluorophenyl 564 CH2CH(CH3)2 H O CH2CH3 F 4-fluorophenyl 565 cyclopropylmethyl H O CH2CH3 F 4-fluorophenyl 566 SCH(CH3)2 H O CH2CH3 F 4-fluorophenyl 567 OCH2CH3 H O CH2CH3 F 4-fluorophenyl 568 (CH2)2 O CH2CH3 F 4-fluorophenyl 569 (CH2)4 O CH2CH3 F 4-fluorophenyl 570 CH3 H O CH2CH3 F 4-chlorophenyl 571 CH2CH3 H O CH2CH3 F 4-chlorophenyl 572 CH2CF3 H O CH2CH3 F 4-chlorophenyl 573 CH2CH2CH3 H O CH2CH3 F 4-chlorophenyl 574 CH2CH(CH3)2 H O CH2CH3 F 4-chlorophenyl 575 cyclopropylmethyl H O CH2CH3 F 4-chlorophenyl 576 SCH(CH3)2 H O CH2CH3 F 4-chlorophenyl 577 OCH2CH3 H O CH2CH3 F 4-chlorophenyl 578 (CH2)2 O CH2CH3 F 4-chlorophenyl 579 (CH2)4 O CH2CH3 F 4-chlorophenyl 580 CH3 H O CH2CH3 F 4-trifluoromethylphenyl 581 CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 582 CH2CF3 H O CH2CH3 F 4-trifluoromethylphenyl 583 CH2CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 584 CH2CH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 585 cyclopropylmethyl H O CH2CH3 F 4-trifluoromethylphenyl 586 SCH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 587 OCH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 588 (CH2)2 O CH2CH3 F 4-trifluoromethylphenyl 589 (CH2)4 O CH2CH3 F 4-trifluoromethylphenyl 590 CH3 H O CH2CH3 F 4-methoxyphenyl 591 CH2CH3 H O CH2CH3 F 4-methoxyphenyl 592 CH2CF3 H O CH2CH3 F 4-methoxyphenyl 593 CH2CH2CH3 H O CH2CH3 F 4-methoxyphenyl 594 CH2CH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 595 cyclopropylmethyl H O CH2CH3 F 4-methoxyphenyl 596 SCH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 597 OCH2CH3 H O CH2CH3 F 4-methoxyphenyl 598 (CH2)2 O CH2CH3 F 4-methoxyphenyl 599 (CH2)4 O CH2CH3 F 4-methoxyphenyl 600 CH3 H O CH2CH3 F 3,4 dichloro phenyl 601 CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 602 CH2CF3 H O CH2CH3 F 3,4 dichloro phenyl 603 CH2CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 604 CH2CH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 605 cyclopropylmethyl H O CH2CH3 F 3,4 dichloro phenyl 606 SCH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 607 OCH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 608 (CH2)2 O CH2CH3 F 3,4 dichloro phenyl 609 (CH2)4 O CH2CH3 F 3,4 dichloro phenyl 610 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 611 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 612 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 613 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 614 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 615 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 616 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 617 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 618 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 619 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 620 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 621 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 622 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 623 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 624 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 625 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 626 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 627 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 628 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 629 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 630 CH3 H O CH2CF3 F 4-fluorophenyl 631 CH2CH3 H O CH2CF3 F 4-fluorophenyl 632 CH2CF3 H O CH2CF3 F 4-fluorophenyl 633 CH2CH2CH3 H O CH2CF3 F 4-fluorophenyl 634 CH2CH(CH3)2 H O CH2CF3 F 4-fluorophenyl 635 cyclopropylmethyl H O CH2CF3 F 4-fluorophenyl 636 SCH(CH3)2 H O CH2CF3 F 4-fluorophenyl 637 OCH2CH3 H O CH2CF3 F 4-fluorophenyl 638 (CH2)2 O CH2CF3 F 4-fluorophenyl 639 (CH2)4 O CH2CF3 F 4-fluorophenyl 640 CH3 H O CH2CF3 F 4-chlorophenyl 641 CH2CH3 H O CH2CF3 F 4-chlorophenyl 642 CH2CF3 H O CH2CF3 F 4-chlorophenyl 643 CH2CH2CH3 H O CH2CF3 F 4-chlorophenyl 644 CH2CH(CH3)2 H O CH2CF3 F 4-chlorophenyl 645 cyclopropylmethyl H O CH2CF3 F 4-chlorophenyl 646 SCH(CH3)2 H O CH2CF3 F 4-chlorophenyl 647 OCH2CH3 H O CH2CF3 F 4-chlorophenyl 648 (CH2)2 O CH2CF3 F 4-chlorophenyl 649 (CH2)4 O CH2CF3 F 4-chlorophenyl 650 CH3 H O CH2CF3 F 4-trifluoromethylphenyl 651 CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 652 CH2CF3 H O CH2CF3 F 4-trifluoromethylphenyl 653 CH2CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 654 CH2CH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 655 cyclopropylmethyl H O CH2CF3 F 4-trifluoromethylphenyl 656 SCH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 657 OCH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 658 (CH2)2 O CH2CF3 F 4-trifluoromethylphenyl 659 (CH2)4 O CH2CF3 F 4-trifluoromethylphenyl 660 CH3 H O CH2CF3 F 4-methoxyphenyl 661 CH2CH3 H O CH2CF3 F 4-methoxyphenyl 662 CH2CF3 H O CH2CF3 F 4-methoxyphenyl 663 CH2CH2CH3 H O CH2CF3 F 4-methoxyphenyl 664 CH2CH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 665 cyclopropylmethyl H O CH2CF3 F 4-methoxyphenyl 666 SCH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 667 OCH2CH3 H O CH2CF3 F 4-methoxyphenyl 668 (CH2)2 O CH2CF3 F 4-methoxyphenyl 669 (CH2)4 O CH2CF3 F 4-methoxyphenyl 670 CH3 H O CH2CF3 F 3,4 dichloro phenyl 671 CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 672 CH2CF3 H O CH2CF3 F 3,4 dichloro phenyl 673 CH2CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 674 CH2CH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 675 cyclopropylmethyl H O CH2CF3 F 3,4 dichloro phenyl 676 SCH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 677 OCH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 678 (CH2)2 O CH2CF3 F 3,4 dichloro phenyl 679 (CH2)4 O CH2CF3 F 3,4 dichloro phenyl 680 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 681 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 682 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 683 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 684 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 685 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 686 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 687 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 688 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 689 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 690 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 691 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 692 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 693 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 694 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 695 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 696 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 697 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 698 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 699 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 700 CH3 H O CH2—c-Pr F 4-fluorophenyl 701 CH2CH3 H O CH2—c-Pr F 4-fluorophenyl 702 CH2CF3 H O CH2—c-Pr F 4-fluorophenyl 703 CH2CH2CH3 H O CH2—c-Pr F 4-fluorophenyl 704 CH2CH(CH3)2 H O CH2—c-Pr F 4-fluorophenyl 705 cyclopropylmethyl H O CH2—c-Pr F 4-fluorophenyl 706 SCH(CH3)2 H O CH2—c-Pr F 4-fluorophenyl 707 OCH2CH3 H O CH2—c-Pr F 4-fluorophenyl 708 (CH2)2 O CH2—c-Pr F 4-fluorophenyl 709 (CH2)4 O CH2—c-Pr F 4-fluorophenyl 710 CH3 H O CH2—c-Pr F 4-chlorophenyl 711 CH2CH3 H O CH2—c-Pr F 4-chlorophenyl 712 CH2CF3 H O CH2—c-Pr F 4-chlorophenyl 713 CH2CH2CH3 H O CH2—c-Pr F 4-chlorophenyl 714 CH2CH(CH3)2 H O CH2—c-Pr F 4-chlorophenyl 715 cyclopropylmethyl H O CH2—c-Pr F 4-chlorophenyl 716 SCH(CH3)2 H O CH2—c-Pr F 4-chlorophenyl 717 OCH2CH3 H O CH2—c-Pr F 4-chlorophenyl 718 (CH2)2 O CH2—c-Pr F 4-chlorophenyl 719 (CH2)4 O CH2—c-Pr F 4-chlorophenyl 720 CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 721 CH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 722 CH2CF3 H O CH2—c-Pr F 4-trifluoromethylphenyl 723 CH2CH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 724 CH2CH(CH3)2 H O CH2—c-Pr F 4-trifluoromethylphenyl 725 cyclopropylmethyl H O CH2—c-Pr F 4-trifluoromethylphenyl 726 SCH(CH3)2 H O CH2—c-Pr F 4-trifluoromethylphenyl 727 OCH2CH3 H O CH2—c-Pr F 4-trifluoromethylphenyl 728 (CH2)2 O CH2—c-Pr F 4-trifluoromethylphenyl 729 (CH2)4 O CH2—c-Pr F 4-trifluoromethylphenyl 730 CH3 H O CH2—c-Pr F 4-methoxyphenyl 731 CH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 732 CH2CF3 H O CH2—c-Pr F 4-methoxyphenyl 733 CH2CH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 734 CH2CH(CH3)2 H O CH2—c-Pr F 4-methoxyphenyl 735 cyclopropylmethyl H O CH2—c-Pr F 4-methoxyphenyl 736 SCH(CH3)2 H O CH2—c-Pr F 4-methoxyphenyl 737 OCH2CH3 H O CH2—c-Pr F 4-methoxyphenyl 738 (CH2)2 O CH2—c-Pr F 4-methoxyphenyl 739 (CH2)4 O CH2—c-Pr F 4-methoxyphenyl 740 CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 741 CH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 742 CH2CF3 H O CH2—c-Pr F 3,4 dichloro phenyl 743 CH2CH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 744 CH2CH(CH3)2 H O CH2—c-Pr F 3,4 dichloro phenyl 745 cyclopropylmethyl H O CH2—c-Pr F 3,4 dichloro phenyl 746 SCH(CH3)2 H O CH2—c-Pr F 3,4 dichloro phenyl 747 OCH2CH3 H O CH2—c-Pr F 3,4 dichloro phenyl 748 (CH2)2 O CH2—c-Pr F 3,4 dichloro phenyl 749 (CH2)4 O CH2—c-Pr F 3,4 dichloro phenyl 750 CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 751 CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 752 CH2CF3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 753 CH2CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 754 CH2CH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 755 cyclopropylmethyl H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 756 SCH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 757 OCH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 758 (CH2)2 O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 759 (CH2)4 O CH2—c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 760 CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 761 CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 762 CH2CF3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 763 CH2CH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 764 CH2CH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 765 cyclopropylmethyl H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 766 SCH(CH3)2 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 767 OCH2CH3 H O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 768 (CH2)2 O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 769 (CH2)4 O CH2—c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 770 CH3 H O CH2CH3 Cl 4-fluorophenyl 771 CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 772 CH2CF3 H O CH2CH3 Cl 4-fluorophenyl 773 CH2CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 774 CH2CH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 775 cyclopropylmethyl H O CH2CH3 Cl 4-fluorophenyl 776 SCH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 777 OCH2CH3 H O CH2CH3 Cl 4-fluorophenyl 778 (CH2)2 O CH2CH3 Cl 4-fluorophenyl 779 (CH2)4 O CH2CH3 Cl 4-fluorophenyl 780 CH3 H O CH2CH3 Cl 4-chlorophenyl 781 CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 782 CH2CF3 H O CH2CH3 Cl 4-chlorophenyl 783 CH2CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 784 CH2CH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 785 cyclopropylmethyl H O CH2CH3 Cl 4-chlorophenyl 786 SCH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 787 OCH2CH3 H O CH2CH3 Cl 4-chlorophenyl 788 (CH2)2 O CH2CH3 Cl 4-chlorophenyl 789 (CH2)4 O CH2CH3 Cl 4-chlorophenyl 790 CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 791 CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 792 CH2CF3 H O CH2CH3 Cl 4-trifluoromethylphenyl 793 CH2CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 794 CH2CH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 795 cyclopropylmethyl H O CH2CH3 Cl 4-trifluoromethylphenyl 796 SCH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 797 OCH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 798 (CH2)2 O CH2CH3 Cl 4-trifluoromethylphenyl 799 (CH2)4 O CH2CH3 Cl 4-trifluoromethylphenyl 800 CH3 H O CH2CH3 Cl 4-methoxyphenyl 801 CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 802 CH2CF3 H O CH2CH3 Cl 4-methoxyphenyl 803 CH2CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 804 CH2CH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 805 cyclopropylmethyl H O CH2CH3 Cl 4-methoxyphenyl 806 SCH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 807 OCH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 808 (CH2)2 O CH2CH3 Cl 4-methoxyphenyl 809 (CH2)4 O CH2CH3 Cl 4-methoxyphenyl 810 CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 811 CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 812 CH2CF3 H O CH2CH3 Cl 3,4 dichloro phenyl 813 CH2CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 814 CH2CH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 815 cyclopropylmethyl H O CH2CH3 Cl 3,4 dichloro phenyl 816 SCH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 817 OCH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 818 (CH2)2 O CH2CH3 Cl 3,4 dichloro phenyl 819 (CH2)4 O CH2CH3 Cl 3,4 dichloro phenyl 820 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 821 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 822 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 823 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 824 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 825 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 826 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 827 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 828 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 829 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 830 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 831 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 832 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 833 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 834 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 835 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 836 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 837 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 838 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 839 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 840 CH3 H O CH2CF3 Cl 4-fluorophenyl 841 CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 842 CH2CF3 H O CH2CF3 Cl 4-fluorophenyl 843 CH2CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 844 CH2CH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 845 cyclopropylmethyl H O CH2CF3 Cl 4-fluorophenyl 846 SCH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 847 OCH2CH3 H O CH2CF3 Cl 4-fluorophenyl 848 (CH2)2 O O CH2CF3 Cl 4-fluorophenyl 849 (CH2)4 O O CH2CF3 Cl 4-fluorophenyl 850 CH3 H O CH2CF3 Cl 4-chlorophenyl 851 CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 852 CH2CF3 H O CH2CF3 Cl 4-chlorophenyl 853 CH2CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 854 CH2CH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 855 cyclopropylmethyl H O CH2CF3 Cl 4-chlorophenyl 856 SCH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 857 OCH2CH3 H O CH2CF3 Cl 4-chlorophenyl 858 (CH2)2 O CH2CF3 Cl 4-chlorophenyl 859 (CH2)4 O CH2CF3 Cl 4-chlorophenyl 860 CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 861 CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 862 CH2CF3 H O CH2CF3 Cl 4-trifluoromethylphenyl 863 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 864 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 865 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethylphenyl 866 SCH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 867 OCH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 868 (CH2)2 O CH2CF3 Cl 4-trifluoromethylphenyl 869 (CH2)4 O CH2CF3 Cl 4-trifluoromethylphenyl 870 CH3 H O CH2CF3 Cl 4-methoxyphenyl 871 CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 872 CH2CF3 H O CH2CF3 Cl 4-methoxyphenyl 873 CH2CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 874 CH2CH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 875 cyclopropylmethyl H O CH2CF3 Cl 4-methoxyphenyl 876 SCH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 877 OCH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 878 (CH2)2 O CH2CF3 Cl 4-methoxyphenyl 879 (CH2)4 O CH2CF3 Cl 4-methoxyphenyl 880 CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 881 CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 882 CH2CF3 H O CH2CF3 Cl 3,4 dichloro phenyl 883 CH2CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 884 CH2CH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 885 cyclopropylmethyl H O CH2CF3 Cl 3,4 dichloro phenyl 886 SCH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 887 OCH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 888 (CH2)2 O CH2CF3 Cl 3,4 dichloro phenyl 889 (CH2)4 O CH2CF3 Cl 3,4 dichloro phenyl 890 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 891 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 892 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 893 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 894 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 895 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 896 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 897 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 898 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 899 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 900 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 901 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 902 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 903 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 904 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 905 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 906 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 907 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 908 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 909 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 910 CH3 H O CH2—c-Pr Cl 4-fluorophenyl 911 CH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 912 CH2CF3 H O CH2—c-Pr Cl 4-fluorophenyl 913 CH2CH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 914 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-fluorophenyl 915 cyclopropylmethyl H O CH2—c-Pr Cl 4-fluorophenyl 916 SCH(CH3)2 H O CH2—c-Pr Cl 4-fluorophenyl 917 OCH2CH3 H O CH2—c-Pr Cl 4-fluorophenyl 918 (CH2)2 O CH2—c-Pr Cl 4-fluorophenyl 919 (CH2)4 O CH2—c-Pr Cl 4-fluorophenyl 920 CH3 H O CH2—c-Pr Cl 4-chlorophenyl 921 CH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 922 CH2CF3 H O CH2—c-Pr Cl 4-chlorophenyl 923 CH2CH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 924 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-chlorophenyl 925 cyclopropylmethyl H O CH2—c-Pr Cl 4-chlorophenyl 926 SCH(CH3)2 H O CH2—c-Pr Cl 4-chlorophenyl 927 OCH2CH3 H O CH2—c-Pr Cl 4-chlorophenyl 928 (CH2)2 O CH2—c-Pr Cl 4-chlorophenyl 929 (CH2)4 O CH2—c-Pr Cl 4-chlorophenyl 930 CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 931 CH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 932 CH2CF3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 933 CH2CH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 934 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 935 cyclopropylmethyl H O CH2—c-Pr Cl 4-trifluoromethylphenyl 936 SCH(CH3)2 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 937 OCH2CH3 H O CH2—c-Pr Cl 4-trifluoromethylphenyl 938 (CH2)2 O CH2—c-Pr Cl 4-trifluoromethylphenyl 939 (CH2)4 O CH2—c-Pr Cl 4-trifluoromethylphenyl 940 CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 941 CH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 942 CH2CF3 H O CH2—c-Pr Cl 4-methoxyphenyl 943 CH2CH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 944 CH2CH(CH3)2 H O CH2—c-Pr Cl 4-methoxyphenyl 945 cyclopropylmethyl H O CH2—c-Pr Cl 4-methoxyphenyl 946 SCH(CH3)2 H O CH2—c-Pr Cl 4-methoxyphenyl 947 OCH2CH3 H O CH2—c-Pr Cl 4-methoxyphenyl 948 (CH2)2 O CH2—c-Pr Cl 4-methoxyphenyl 949 (CH2)4 O CH2—c-Pr Cl 4-methoxyphenyl 950 CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 951 CH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 952 CH2CF3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 953 CH2CH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 954 CH2CH(CH3)2 H O CH2—c-Pr Cl 3,4 dichloro phenyl 955 cyclopropylmethyl H O CH2—c-Pr Cl 3,4 dichloro phenyl 956 SCH(CH3)2 H O CH2—c-Pr Cl 3,4 dichloro phenyl 957 OCH2CH3 H O CH2—c-Pr Cl 3,4 dichloro phenyl 958 (CH2)2 O CH2—c-Pr Cl 3,4 dichloro phenyl 959 (CH2)4 O CH2—c-Pr Cl 3,4 dichloro phenyl 960 CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 961 CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 962 CH2CF3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 963 CH2CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 964 CH2CH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 965 cyclopropylmethyl H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 966 SCH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 967 OCH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 968 (CH2)2 O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 969 (CH2)4 O CH2—c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 970 CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 971 CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 972 CH2CF3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 973 CH2CH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 974 CH2CH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 975 cyclopropylmethyl H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 976 SCH(CH3)2 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 977 OCH2CH3 H O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 978 (CH2)2 O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 979 (CH2)4 O CH2—c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl Compounds of Formula III Formula III Ex R1 R2 Y R4 R5 Z 980 CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 981 CH2CF3 H O CH2CF3 CF3 4-trifluoromethylphenyl 982 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 983 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethylphenyl 984 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 985 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 986 (CH2)2 O CH2CF3 CF3 4-trifluoromethylphenyl 987 (CH2)3 O CH2CF3 CF3 4-trifluoromethylphenyl 988 (CH2)4 O CH2CF3 CF3 4-trifluoromethylphenyl 989 (CH2)5 O CH2CF3 CF3 4-trifluoromethylphenyl 990 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethylphenyl 991 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethylphenyl 992 CH2CH3 H O CH2CF3 CF3 4-tolyl 993 CH2CF3 H O CH2CF3 CF3 4-tolyl 994 CH2CH2CH3 H O CH2CF3 CF3 4-tolyl 995 CH2CH(CH3)2 H O CH2CF3 CF3 4-tolyl 996 cyclopropylmethyl H O CH2CF3 CF3 4-tolyl 997 cyclobutylmethyl H O CH2CF3 CF3 4-tolyl 998 (CH2)2 O CH2CF3 CF3 4-tolyl 999 (CH2)3 O CH2CF3 CF3 4-tolyl 1000 (CH2)4 O CH2CF3 CF3 4-tolyl 1001 (CH2)5 O CH2CF3 CF3 4-tolyl 1002 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-tolyl 1003 Cyclopentyl H O CH2CF3 CF3 4-tolyl 1004 CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1005 CH2CF3 H O CH2CF3 CF3 4-ethyl phenyl 1006 CH2CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1007 CH2CH(CH3)2 H O CH2CF3 CF3 4-ethyl phenyl 1008 cyclopropylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1009 cyclobutylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1010 (CH2)2 O CH2CF3 CF3 4-ethyl phenyl 1011 (CH2)3 O CH2CF3 CF3 4-ethyl phenyl 1012 (CH2)4 O CH2CF3 CF3 4-ethyl phenyl 1013 (CH2)5 O CH2CF3 CF3 4-ethyl phenyl 1014 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-ethyl phenyl 1015 Cyclopentyl H O CH2CF3 CF3 4-ethyl phenyl 1016 CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1017 CH2CF3 H O CH2CF3 CF3 4-isopropyl phenyl 1018 CH2CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1019 CH2CH(CH3)2 H O CH2CF3 CF3 4-isopropyl phenyl 1020 cyclopropylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1021 cyclobutylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1022 (CH2)2 O CH2CF3 CF3 4-isopropyl phenyl 1023 (CH2)3 O CH2CF3 CF3 4-isopropyl phenyl 1024 (CH2)4 O CH2CF3 CF3 4-isopropyl phenyl 1025 (CH2)5 O CH2CF3 CF3 4-isopropyl phenyl 1026 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-isopropyl phenyl 1027 Cyclopentyl H O CH2CF3 CF3 4-isopropyl phenyl 1028 CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1029 CH2CF3 H O CH2CF3 CF3 4-thiomethylphenyl 1030 CH2CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1031 CH2CH(CH3)2 H O CH2CF3 CF3 4-thiomethylphenyl 1032 cyclopropylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1033 cyclobutylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1034 (CH2)2 O CH2CF3 CF3 4-thiomethylphenyl 1035 (CH2)3 O CH2CF3 CF3 4-thiomethylphenyl 1036 (CH2)4 O CH2CF3 CF3 4-thiomethylphenyl 1037 (CH2)5 O CH2CF3 CF3 4-thiomethylphenyl 1038 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-thiomethylphenyl 1039 Cyclopentyl H O CH2CF3 CF3 4-thiomethylphenyl 1040 CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1041 CH2CF3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1042 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1043 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1044 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1045 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1046 (CH2)2 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1047 (CH2)3 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1048 (CH2)4 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1049 (CH2)5 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1050 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethoxyphenyl 1051 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1052 CH2CH3 H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1053 CH2CF3 H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1054 CH2CH2CH3 H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1055 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1056 cyclopropylmethyl H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1057 cyclobutylmethyl H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1058 (CH2)2 O CH2—c-Pr CF3 4-trifluoromethylphenyl 1059 (CH2)3 O CH2—c-Pr CF3 4-trifluoromethylphenyl 1060 (CH2)4 O CH2—c-Pr CF3 4-trifluoromethylphenyl 1061 (CH2)5 O CH2—c-Pr CF3 4-trifluoromethylphenyl 1062 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-trifluoromethylphenyl 1063 Cyclopentyl H O CH2—c-Pr CF3 4-trifluoromethylphenyl 1064 CH2CH3 H O CH2—c-Pr CF3 4-tolyl 1065 CH2CF3 H O CH2—c-Pr CF3 4-tolyl 1066 CH2CH2CH3 H O CH2—c-Pr CF3 4-tolyl 1067 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-tolyl 1068 cyclopropylmethyl H O CH2—c-Pr CF3 4-tolyl 1069 cyclobutylmethyl H O CH2—c-Pr CF3 4-tolyl 1070 (CH2)2 O CH2—c-Pr CF3 4-tolyl 1071 (CH2)3 O CH2—c-Pr CF3 4-tolyl 1072 (CH2)4 O CH2—c-Pr CF3 4-tolyl 1073 (CH2)5 O CH2—c-Pr CF3 4-tolyl 1074 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-tolyl 1075 Cyclopentyl H O CH2—c-Pr CF3 4-tolyl 1076 CH2CH3 H O CH2—c-Pr CF3 4-ethyl phenyl 1077 CH2CF3 H O CH2—c-Pr CF3 4-ethyl phenyl 1078 CH2CH2CH3 H O CH2—c-Pr CF3 4-ethyl phenyl 1079 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-ethyl phenyl 1080 cyclopropylmethyl H O CH2—c-Pr CF3 4-ethyl phenyl 1081 cyclobutylmethyl H O CH2—c-Pr CF3 4-ethyl phenyl 1082 (CH2)2 O CH2—c-Pr CF3 4-ethyl phenyl 1083 (CH2)3 O CH2—c-Pr CF3 4-ethyl phenyl 1084 (CH2)4 O CH2—c-Pr CF3 4-ethyl phenyl 1085 (CH2)5 O CH2—c-Pr CF3 4-ethyl phenyl 1086 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-ethyl phenyl 1087 Cyclopentyl H O CH2—c-Pr CF3 4-ethyl phenyl 1088 CH2CH3 H O CH2—c-Pr CF3 4-isopropyl phenyl 1089 CH2CF3 H O CH2—c-Pr CF3 4-isopropyl phenyl 1090 CH2CH2CH3 H O CH2—c-Pr CF3 4-isopropyl phenyl 1091 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-isopropyl phenyl 1092 cyclopropylmethyl H O CH2—c-Pr CF3 4-isopropyl phenyl 1093 cyclobutylmethyl H O CH2—c-Pr CF3 4-isopropyl phenyl 1094 (CH2)2 O CH2—c-Pr CF3 4-isopropyl phenyl 1095 (CH2)3 O CH2—c-Pr CF3 4-isopropyl phenyl 1096 (CH2)4 O CH2—c-Pr CF3 4-isopropyl phenyl 1097 (CH2)5 O CH2—c-Pr CF3 4-isopropyl phenyl 1098 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-isopropyl phenyl 1099 Cyclopentyl H O CH2—c-Pr CF3 4-isopropyl phenyl 1100 CH2CH3 H O CH2—c-Pr CF3 4-thiomethylphenyl 1101 CH2CF3 H O CH2—c-Pr CF3 4-thiomethylphenyl 1102 CH2CH2CH3 H O CH2—c-Pr CF3 4-thiomethylphenyl 1103 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-thiomethylphenyl 1104 cyclopropylmethyl H O CH2—c-Pr CF3 4-thiomethylphenyl 1105 cyclobutylmethyl H O CH2—c-Pr CF3 4-thiomethylphenyl 1106 (CH2)2 O CH2—c-Pr CF3 4-thiomethylphenyl 1107 (CH2)3 O CH2—c-Pr CF3 4-thiomethylphenyl 1108 (CH2)4 O CH2—c-Pr CF3 4-thiomethylphenyl 1109 (CH2)5 O CH2—c-Pr CF3 4-thiomethylphenyl 1110 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-thiomethylphenyl 1111 Cyclopentyl H O CH2—c-Pr CF3 4-thiomethylphenyl 1112 CH2CH3 H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1113 CH2CF3 H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1114 CH2CH2CH3 H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1115 CH2CH(CH3)2 H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1116 cyclopropylmethyl H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1117 cyclobutylmethyl H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1118 (CH2)2 O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1119 (CH2)3 O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1120 (CH2)4 O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1121 (CH2)5 O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1122 5,5-spiro[2.3]hexane O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1123 Cyclopentyl H O CH2—c-Pr CF3 4-trifluoromethoxyphenyl 1124 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1125 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1126 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1127 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1128 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1129 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1130 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1131 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1132 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1133 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1134 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1135 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1136 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1137 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1138 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1139 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1140 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1141 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1142 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1143 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1144 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1145 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1146 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1147 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1148 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1149 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1150 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1151 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1152 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1153 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1154 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 1155 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 1156 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 1157 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 1158 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 1159 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1160 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1161 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1162 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1163 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1164 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1165 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1166 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1167 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1168 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1169 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1170 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 1171 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1172 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1173 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1174 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1175 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1176 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1177 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1178 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1179 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1180 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1181 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1182 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 1183 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1184 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1185 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1186 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1187 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1188 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1189 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1190 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1191 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1192 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1193 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1194 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1195 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1196 CH2CH3 H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1197 CH2CF3 H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1198 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1199 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1200 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1201 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1202 (CH2)2 O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1203 (CH2)3 O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1204 (CH2)4 O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1205 (CH2)5 O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1206 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1207 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-trifluoromethylphenyl 1208 CH2CH3 H O CH2—c-Pr OCH2CF3 4-tolyl 1209 CH2CF3 H O CH2—c-Pr OCH2CF3 4-tolyl 1210 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-tolyl 1211 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-tolyl 1212 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-tolyl 1213 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-tolyl 1214 (CH2)2 O CH2—c-Pr OCH2CF3 4-tolyl 1215 (CH2)3 O CH2—c-Pr OCH2CF3 4-tolyl 1216 (CH2)4 O CH2—c-Pr OCH2CF3 4-tolyl 1217 (CH2)5 O CH2—c-Pr OCH2CF3 4-tolyl 1218 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-tolyl 1219 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-tolyl 1220 CH2CH3 H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1221 CH2CF3 H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1222 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1223 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1224 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1225 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1226 (CH2)2 O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1227 (CH2)3 O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1228 (CH2)4 O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1229 (CH2)5 O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1230 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1231 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-ethyl phenyl 1232 CH2CH3 H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1233 CH2CF3 H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1234 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1235 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1236 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1237 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1238 (CH2)2 O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1239 (CH2)3 O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1240 (CH2)4 O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1241 (CH2)5 O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1242 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1243 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-isopropyl phenyl 1244 CH2CH3 H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1245 CH2CF3 H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1246 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1247 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1248 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1249 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1250 (CH2)2 O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1251 (CH2)3 O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1252 (CH2)4 O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1253 (CH2)5 O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1254 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1255 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-thiomethylphenyl 1256 CH2CH3 H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1257 CH2CF3 H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1258 CH2CH2CH3 H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1259 CH2CH(CH3)2 H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1260 cyclopropylmethyl H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1261 cyclobutylmethyl H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1262 (CH2)2 O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1263 (CH2)3 O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1264 (CH2)4 O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1265 (CH2)5 O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1266 5,5-spiro[2.3]hexane O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1267 Cyclopentyl H O CH2—c-Pr OCH2CF3 4-trifluoromethoxyphenyl Compounds of Formula III Formula III Ex R1 R2 Y R4 R5 Z 1268 cyclobutylmethyl H O CH2CF3 Cl 4-trifluoromethylphenyl 1269 (CH2)3 O CH2CF3 Cl 4-trifluoromethylphenyl 1270 (CH2)5 O CH2CF3 Cl 4-trifluoromethylphenyl 1271 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethylphenyl 1272 Cyclopentyl H O CH2CF3 Cl 4-trifluoromethylphenyl 1273 CH2CH3 H O CH2CF3 Cl 4-tolyl 1274 CH2CF3 H O CH2CF3 Cl 4-tolyl 1275 CH2CH2CH3 H O CH2CF3 Cl 4-tolyl 1276 CH2CH(CH3)2 H O CH2CF3 Cl 4-tolyl 1277 cyclopropylmethyl H O CH2CF3 Cl 4-tolyl 1278 cyclobutylmethyl H O CH2CF3 Cl 4-tolyl 1279 (CH2)2 O CH2CF3 Cl 4-tolyl 1280 (CH2)3 O CH2CF3 Cl 4-tolyl 1281 (CH2)4 O CH2CF3 Cl 4-tolyl 1282 (CH2)5 O CH2CF3 Cl 4-tolyl 1283 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-tolyl 1284 Cyclopentyl H O CH2CF3 Cl 4-tolyl 1285 CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1286 CH2CF3 H O CH2CF3 Cl 4-ethyl phenyl 1287 CH2CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1288 CH2CH(CH3)2 H O CH2CF3 Cl 4-ethyl phenyl 1289 cyclopropylmethyl H O CH2CF3 Cl 4-ethyl phenyl 1290 cyclobutylmethyl H O CH2CF3 Cl 4-ethyl phenyl 1291 (CH2)2 O CH2CF3 Cl 4-ethyl phenyl 1292 (CH2)3 O CH2CF3 Cl 4-ethyl phenyl 1293 (CH2)4 O CH2CF3 Cl 4-ethyl phenyl 1294 (CH2)5 O CH2CF3 Cl 4-ethyl phenyl 1295 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-ethyl phenyl 1296 Cyclopentyl H O CH2CF3 Cl 4-ethyl phenyl 1297 CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1298 CH2CF3 H O CH2CF3 Cl 4-isopropyl phenyl 1299 CH2CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1300 CH2CH(CH3)2 H O CH2CF3 Cl 4-isopropyl phenyl 1301 cyclopropylmethyl H O CH2CF3 Cl 4-isopropyl phenyl 1302 cyclobutylmethyl H O CH2CF3 Cl 4-isopropyl phenyl 1303 (CH2)2 O CH2CF3 Cl 4-isopropyl phenyl 1304 (CH2)3 O CH2CF3 Cl 4-isopropyl phenyl 1305 (CH2)4 O CH2CF3 Cl 4-isopropyl phenyl 1306 (CH2)5 O CH2CF3 Cl 4-isopropyl phenyl 1307 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-isopropyl phenyl 1308 Cyclopentyl H O CH2CF3 Cl 4-isopropyl phenyl 1309 CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1310 CH2CF3 H O CH2CF3 Cl 4-thiomethylphenyl 1311 CH2CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1312 CH2CH(CH3)2 H O CH2CF3 Cl 4-thiomethylphenyl 1313 cyclopropylmethyl H O CH2CF3 Cl 4-thiomethylphenyl 1314 cyclobutylmethyl H O CH2CF3 Cl 4-thiomethylphenyl 1315 (CH2)2 O CH2CF3 Cl 4-thiomethylphenyl 1316 (CH2)3 O CH2CF3 Cl 4-thiomethylphenyl 1317 (CH2)4 O CH2CF3 Cl 4-thiomethylphenyl 1318 (CH2)5 O CH2CF3 Cl 4-thiomethylphenyl 1319 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-thiomethylphenyl 1320 Cyclopentyl H O CH2CF3 Cl 4-thiomethylphenyl 1321 CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1322 CH2CF3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1323 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1324 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1325 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1326 cyclobutylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1327 (CH2)2 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1328 (CH2)3 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1329 (CH2)4 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1330 (CH2)5 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1331 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethoxyphenyl 1332 Cyclopentyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1333 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1334 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1335 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1336 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethylphenyl 1337 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1338 CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1339 CH2CF3 H O CH2-c-Pr Cl 4-tolyl 1340 CH2CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1341 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-tolyl 1342 cyclopropylmethyl H O CH2-c-Pr Cl 4-tolyl 1343 cyclobutylmethyl H O CH2-c-Pr Cl 4-tolyl 1344 (CH2)2 O CH2-c-Pr Cl 4-tolyl 1345 (CH2)3 O CH2-c-Pr Cl 4-tolyl 1346 (CH2)4 O CH2-c-Pr Cl 4-tolyl 1347 (CH2)5 O CH2-c-Pr Cl 4-tolyl 1348 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-tolyl 1349 Cyclopentyl H O CH2-c-Pr Cl 4-tolyl 1350 CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1351 CH2CF3 H O CH2-c-Pr Cl 4-ethyl phenyl 1352 CH2CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1353 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-ethyl phenyl 1354 cyclopropylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1355 cyclobutylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1356 (CH2)2 O CH2-c-Pr Cl 4-ethyl phenyl 1357 (CH2)3 O CH2-c-Pr Cl 4-ethyl phenyl 1358 (CH2)4 O CH2-c-Pr Cl 4-ethyl phenyl 1359 (CH2)5 O CH2-c-Pr Cl 4-ethyl phenyl 1360 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-ethyl phenyl 1361 Cyclopentyl H O CH2-c-Pr Cl 4-ethyl phenyl 1362 CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1363 CH2CF3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1364 CH2CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1365 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-isopropyl phenyl 1366 cyclopropylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1367 cyclobutylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1368 (CH2)2 O CH2-c-Pr Cl 4-isopropyl phenyl 1369 (CH2)3 O CH2-c-Pr Cl 4-isopropyl phenyl 1370 (CH2)4 O CH2-c-Pr Cl 4-isopropyl phenyl 1371 (CH2)5 O CH2-c-Pr Cl 4-isopropyl phenyl 1372 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-isopropyl phenyl 1373 Cyclopentyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1374 CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1375 CH2CF3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1376 CH2CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1377 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-thiomethylphenyl 1378 cyclopropylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1379 cyclobutylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1380 (CH2)2 O CH2-c-Pr Cl 4-thiomethylphenyl 1381 (CH2)3 O CH2-c-Pr Cl 4-thiomethylphenyl 1382 (CH2)4 O CH2-c-Pr Cl 4-thiomethylphenyl 1383 (CH2)5 O CH2-c-Pr Cl 4-thiomethylphenyl 1384 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-thiomethylphenyl 1385 Cyclopentyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1386 CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1387 CH2CF3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1388 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1389 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1390 cyclopropylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1391 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1392 (CH2)2 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1393 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1394 (CH2)4 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1395 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1396 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1397 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1398 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1399 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1400 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1401 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1402 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1403 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1404 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1405 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1406 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1407 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1408 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1409 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1410 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1411 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1412 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1413 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1414 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1415 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1416 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1417 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1418 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1419 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1420 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1421 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1422 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1423 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1424 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1425 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1426 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1427 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1428 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 1429 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 1430 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 1431 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 1432 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 1433 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1434 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1435 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1436 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1437 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1438 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1439 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1440 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1441 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1442 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1443 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1444 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 1445 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1446 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1447 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1448 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1449 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1450 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1451 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1452 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1453 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1454 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1455 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1456 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 1457 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1458 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1459 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1460 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1461 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1462 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1463 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1464 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1465 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1466 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1467 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1468 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1469 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1470 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1471 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1472 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1473 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1474 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1475 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1476 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1477 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1478 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1479 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1480 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1481 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1482 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1483 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 1484 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1485 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 1486 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1487 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1488 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 1489 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 1490 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 1491 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 1492 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 1493 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 1494 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1495 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1496 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1497 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1498 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1499 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1500 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1501 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1502 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1503 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1504 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1505 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1506 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1507 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1508 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1509 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1510 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1511 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1512 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1513 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1514 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1515 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1516 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1517 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1518 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1519 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1520 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1521 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1522 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1523 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1524 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1525 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1526 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1527 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1528 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1529 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1530 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1531 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1532 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1533 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1534 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1535 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1536 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1537 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1538 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1539 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1540 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl Compounds of Formula IV Formula IV Ex R1 R2 X R3 R5 Z 1541 CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 1542 CH2CF3 H O CH2CF3 CF3 4-trifluoromethylphenyl 1543 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 1544 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethylphenyl 1545 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 1546 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 1547 (CH2)2 O CH2CF3 CF3 4-trifluoromethylphenyl 1548 (CH2)3 O CH2CF3 CF3 4-trifluoromethylphenyl 1549 (CH2)4 O CH2CF3 CF3 4-trifluoromethylphenyl 1550 (CH2)5 O CH2CF3 CF3 4-trifluoromethylphenyl 1551 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethylphenyl 1552 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethylphenyl 1553 CH2CH3 H O CH2CF3 CF3 4-tolyl 1554 CH2CF3 H O CH2CF3 CF3 4-tolyl 1555 CH2CH2CH3 H O CH2CF3 CF3 4-tolyl 1556 CH2CH(CH3)2 H O CH2CF3 CF3 4-tolyl 1557 cyclopropylmethyl H O CH2CF3 CF3 4-tolyl 1558 cyclobutylmethyl H O CH2CF3 CF3 4-tolyl 1559 (CH2)2 O CH2CF3 CF3 4-tolyl 1560 (CH2)3 O CH2CF3 CF3 4-tolyl 1561 (CH2)4 O CH2CF3 CF3 4-tolyl 1562 (CH2)5 O CH2CF3 CF3 4-tolyl 1563 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-tolyl 1564 Cyclopentyl H O CH2CF3 CF3 4-tolyl 1565 CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1566 CH2CF3 H O CH2CF3 CF3 4-ethyl phenyl 1567 CH2CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1568 CH2CH(CH3)2 H O CH2CF3 CF3 4-ethyl phenyl 1569 cyclopropylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1570 cyclobutylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1571 (CH2)2 O CH2CF3 CF3 4-ethyl phenyl 1572 (CH2)3 O CH2CF3 CF3 4-ethyl phenyl 1573 (CH2)4 O CH2CF3 CF3 4-ethyl phenyl 1574 (CH2)5 O CH2CF3 CF3 4-ethyl phenyl 1575 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-ethyl phenyl 1576 Cyclopentyl H O CH2CF3 CF3 4-ethyl phenyl 1577 CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1578 CH2CF3 H O CH2CF3 CF3 4-isopropyl phenyl 1579 CH2CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1580 CH2CH(CH3)2 H O CH2CF3 CF3 4-isopropyl phenyl 1581 cyclopropylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1582 cyclobutylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1583 (CH2)2 O CH2CF3 CF3 4-isopropyl phenyl 1584 (CH2)3 O CH2CF3 CF3 4-isopropyl phenyl 1585 (CH2)4 O CH2CF3 CF3 4-isopropyl phenyl 1586 (CH2)5 O CH2CF3 CF3 4-isopropyl phenyl 1587 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-isopropyl phenyl 1588 Cyclopentyl H O CH2CF3 CF3 4-isopropyl phenyl 1589 CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1590 CH2CF3 H O CH2CF3 CF3 4-thiomethylphenyl 1591 CH2CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1592 CH2CH(CH3)2 H O CH2CF3 CF3 4-thiomethylphenyl 1593 cyclopropylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1594 cyclobutylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1595 (CH2)2 O CH2CF3 CF3 4-thiomethylphenyl 1596 (CH2)3 O CH2CF3 CF3 4-thiomethylphenyl 1597 (CH2)4 O CH2CF3 CF3 4-thiomethylphenyl 1598 (CH2)5 O CH2CF3 CF3 4-thiomethylphenyl 1599 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-thiomethylphenyl 1600 Cyclopentyl H O CH2CF3 CF3 4-thiomethylphenyl 1601 CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1602 CH2CF3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1603 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1604 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1605 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1606 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1607 (CH2)2 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1608 (CH2)3 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1609 (CH2)4 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1610 (CH2)5 O CH2CF3 CF3 4-trifluoromethoxyphenyl 1611 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethoxyphenyl 1612 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1613 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1614 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1615 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1616 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1617 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1618 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1619 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1620 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1621 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1622 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1623 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethylphenyl 1624 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1625 CH2CH3 H O CH2-c-Pr CF3 4-tolyl 1626 CH2CF3 H O CH2-c-Pr CF3 4-tolyl 1627 CH2CH2CH3 H O CH2-c-Pr CF3 4-tolyl 1628 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-tolyl 1629 cyclopropylmethyl H O CH2-c-Pr CF3 4-tolyl 1630 cyclobutylmethyl H O CH2-c-Pr CF3 4-tolyl 1631 (CH2)2 O CH2-c-Pr CF3 4-tolyl 1632 (CH2)3 O CH2-c-Pr CF3 4-tolyl 1633 (CH2)4 O CH2-c-Pr CF3 4-tolyl 1634 (CH2)5 O CH2-c-Pr CF3 4-tolyl 1635 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-tolyl 1636 Cyclopentyl H O CH2-c-Pr CF3 4-tolyl 1637 CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 1638 CH2CF3 H O CH2-c-Pr CF3 4-ethyl phenyl 1639 CH2CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 1640 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-ethyl phenyl 1641 cyclopropylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 1642 cyclobutylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 1643 (CH2)2 O CH2-c-Pr CF3 4-ethyl phenyl 1644 (CH2)3 O CH2-c-Pr CF3 4-ethyl phenyl 1645 (CH2)4 O CH2-c-Pr CF3 4-ethyl phenyl 1646 (CH2)5 O CH2-c-Pr CF3 4-ethyl phenyl 1647 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-ethyl phenyl 1648 Cyclopentyl H O CH2-c-Pr CF3 4-ethyl phenyl 1649 CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1650 CH2CF3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1651 CH2CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1652 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-isopropyl phenyl 1653 cyclopropylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1654 cyclobutylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1655 (CH2)2 O CH2-c-Pr CF3 4-isopropyl phenyl 1656 (CH2)3 O CH2-c-Pr CF3 4-isopropyl phenyl 1657 (CH2)4 O CH2-c-Pr CF3 4-isopropyl phenyl 1658 (CH2)5 O CH2-c-Pr CF3 4-isopropyl phenyl 1659 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-isopropyl phenyl 1660 Cyclopentyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1661 CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1662 CH2CF3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1663 CH2CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1664 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-thiomethylphenyl 1665 cyclopropylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1666 cyclobutylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1667 (CH2)2 O CH2-c-Pr CF3 4-thiomethylphenyl 1668 (CH2)3 O CH2-c-Pr CF3 4-thiomethylphenyl 1669 (CH2)4 O CH2-c-Pr CF3 4-thiomethylphenyl 1670 (CH2)5 O CH2-c-Pr CF3 4-thiomethylphenyl 1671 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-thiomethylphenyl 1672 Cyclopentyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1673 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1674 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1675 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1676 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1677 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1678 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1679 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1680 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1681 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1682 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1683 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1684 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1685 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1686 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1687 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1688 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1689 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1690 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1691 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1692 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1693 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1694 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1695 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1696 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1697 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1698 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1699 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1700 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1701 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1702 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1703 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1704 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1705 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1706 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1707 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1708 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1709 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1710 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1711 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1712 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1713 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1714 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1715 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 1716 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 1717 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 1718 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 1719 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 1720 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1721 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1722 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1723 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1724 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1725 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1726 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1727 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1728 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1729 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1730 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1731 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 1732 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1733 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1734 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1735 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1736 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1737 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1738 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1739 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1740 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1741 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1742 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1743 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 1744 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1745 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1746 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1747 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1748 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1749 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1750 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1751 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1752 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1753 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1754 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1755 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1756 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1757 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1758 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1759 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1760 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1761 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1762 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1763 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1764 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1765 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1766 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1767 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1768 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1769 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1770 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 1771 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1772 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 1773 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1774 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1775 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 1776 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 1777 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 1778 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 1779 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 1780 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 1781 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1782 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1783 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1784 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1785 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1786 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1787 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1788 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1789 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1790 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1791 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1792 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1793 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1794 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1795 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1796 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1797 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1798 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1799 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1800 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1801 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1802 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1803 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1804 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1805 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1806 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1807 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1808 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1809 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1810 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1811 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1812 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1813 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1814 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1815 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1816 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1817 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1818 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1819 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1820 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1821 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1822 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1823 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1824 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1825 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1826 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1827 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1828 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl Compounds of Formula IV Formula IV Ex R1 R2 X R3 R5 Z 1829 CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 1830 CH2CF3 H O CH2CF3 Cl 4-trifluoromethylphenyl 1831 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 1832 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 1833 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethylphenyl 1834 cyclobutylmethyl H O CH2CF3 Cl 4-trifluoromethylphenyl 1835 (CH2)2 O CH2CF3 Cl 4-trifluoromethylphenyl 1836 (CH2)3 O CH2CF3 Cl 4-trifluoromethylphenyl 1837 (CH2)4 O CH2CF3 Cl 4-trifluoromethylphenyl 1838 (CH2)5 O CH2CF3 Cl 4-trifluoromethylphenyl 1839 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethylphenyl 1840 Cyclopentyl H O CH2CF3 Cl 4-trifluoromethylphenyl 1841 CH2CH3 H O CH2CF3 Cl 4-tolyl 1842 CH2CF3 H O CH2CF3 Cl 4-tolyl 1843 CH2CH2CH3 H O CH2CF3 Cl 4-tolyl 1844 CH2CH(CH3)2 H O CH2CF3 Cl 4-tolyl 1845 cyclopropylmethyl H O CH2CF3 Cl 4-tolyl 1846 cyclobutylmethyl H O CH2CF3 Cl 4-tolyl 1847 (CH2)2 O CH2CF3 Cl 4-tolyl 1848 (CH2)3 O CH2CF3 Cl 4-tolyl 1849 (CH2)4 O CH2CF3 Cl 4-tolyl 1850 (CH2)5 O CH2CF3 Cl 4-tolyl 1851 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-tolyl 1852 Cyclopentyl H O CH2CF3 Cl 4-tolyl 1853 CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1854 CH2CF3 H O CH2CF3 Cl 4-ethyl phenyl 1855 CH2CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1856 CH2CH(CH3)2 H O CH2CF3 Cl 4-ethyl phenyl 1857 cyclopropylmethyl H O CH2CF3 Cl 4-ethyl phenyl 1858 cyclobutylmethyl H O CH2CF3 Cl 4-ethyl phenyl 1859 (CH2)2 O CH2CF3 Cl 4-ethyl phenyl 1860 (CH2)3 O CH2CF3 Cl 4-ethyl phenyl 1861 (CH2)4 O CH2CF3 Cl 4-ethyl phenyl 1862 (CH2)5 O CH2CF3 Cl 4-ethyl phenyl 1863 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-ethyl phenyl 1864 Cyclopentyl H O CH2CF3 Cl 4-ethyl phenyl 1865 CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1866 CH2CF3 H O CH2CF3 Cl 4-isopropyl phenyl 1867 CH2CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1868 CH2CH(CH3)2 H O CH2CF3 Cl 4-isopropyl phenyl 1869 cyclopropylmethyl H O CH2CF3 Cl 4-isopropyl phenyl 1870 cyclobutylmethyl H O CH2CF3 Cl 4-isopropyl phenyl 1871 (CH2)2 O CH2CF3 Cl 4-isopropyl phenyl 1872 (CH2)3 O CH2CF3 Cl 4-isopropyl phenyl 1873 (CH2)4 O CH2CF3 Cl 4-isopropyl phenyl 1874 (CH2)5 O CH2CF3 Cl 4-isopropyl phenyl 1875 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-isopropyl phenyl 1876 Cyclopentyl H O CH2CF3 Cl 4-isopropyl phenyl 1877 CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1878 CH2CF3 H O CH2CF3 Cl 4-thiomethylphenyl 1879 CH2CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1880 CH2CH(CH3)2 H O CH2CF3 Cl 4-thiomethylphenyl 1881 cyclopropylmethyl H O CH2CF3 Cl 4-thiomethylphenyl 1882 cyclobutylmethyl H O CH2CF3 Cl 4-thiomethylphenyl 1883 (CH2)2 O CH2CF3 Cl 4-thiomethylphenyl 1884 (CH2)3 O CH2CF3 Cl 4-thiomethylphenyl 1885 (CH2)4 O CH2CF3 Cl 4-thiomethylphenyl 1886 (CH2)5 O CH2CF3 Cl 4-thiomethylphenyl 1887 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-thiomethylphenyl 1888 Cyclopentyl H O CH2CF3 Cl 4-thiomethylphenyl 1889 CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1890 CH2CF3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1891 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1892 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1893 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1894 cyclobutylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1895 (CH2)2 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1896 (CH2)3 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1897 (CH2)4 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1898 (CH2)5 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1899 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethoxyphenyl 1900 Cyclopentyl H O CH2CF3 Cl 4-trifluoromethoxylphenyl 1901 CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1902 CH2CF3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1903 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1904 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1905 cyclopropylmethyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1906 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1907 (CH2)2 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1908 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1909 (CH2)4 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1910 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1911 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethylphenyl 1912 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1913 CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1914 CH2CF3 H O CH2-c-Pr Cl 4-tolyl 1915 CH2CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1916 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-tolyl 1917 cyclopropylmethyl H O CH2-c-Pr Cl 4-tolyl 1918 cyclobutylmethyl H O CH2-c-Pr Cl 4-tolyl 1919 (CH2)2 O CH2-c-Pr Cl 4-tolyl 1920 (CH2)3 O CH2-c-Pr Cl 4-tolyl 1921 (CH2)4 O CH2-c-Pr Cl 4-tolyl 1922 (CH2)5 O CH2-c-Pr Cl 4-tolyl 1923 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-tolyl 1924 Cyclopentyl H O CH2-c-Pr Cl 4-tolyl 1925 CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1926 CH2CF3 H O CH2-c-Pr Cl 4-ethyl phenyl 1927 CH2CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1928 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-ethyl phenyl 1929 cyclopropylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1930 cyclobutylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1931 (CH2)2 O CH2-c-Pr Cl 4-ethyl phenyl 1932 (CH2)3 O CH2-c-Pr Cl 4-ethyl phenyl 1933 (CH2)4 O CH2-c-Pr Cl 4-ethyl phenyl 1934 (CH2)5 O CH2-c-Pr Cl 4-ethyl phenyl 1935 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-ethyl phenyl 1936 Cyclopentyl H O CH2-c-Pr Cl 4-ethyl phenyl 1937 CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1938 CH2CF3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1939 CH2CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1940 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-isopropyl phenyl 1941 cyclopropylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1942 cyclobutylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1943 (CH2)2 O CH2-c-Pr Cl 4-isopropyl phenyl 1944 (CH2)3 O CH2-c-Pr Cl 4-isopropyl phenyl 1945 (CH2)4 O CH2-c-Pr Cl 4-isopropyl phenyl 1946 (CH2)5 O CH2-c-Pr Cl 4-isopropyl phenyl 1947 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-isopropyl phenyl 1948 Cyclopentyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1949 CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1950 CH2CF3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1951 CH2CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1952 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-thiomethylphenyl 1953 cyclopropylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1954 cyclobutylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1955 (CH2)2 O CH2-c-Pr Cl 4-thiomethylphenyl 1956 (CH2)3 O CH2-c-Pr Cl 4-thiomethylphenyl 1957 (CH2)4 O CH2-c-Pr Cl 4-thiomethylphenyl 1958 (CH2)5 O CH2-c-Pr Cl 4-thiomethylphenyl 1959 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-thiomethylphenyl 1960 Cyclopentyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1961 CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1962 CH2CF3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1963 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1964 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1965 cyclopropylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1966 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1967 (CH2)2 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1968 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1969 (CH2)4 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1970 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1971 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1972 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1973 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1974 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1975 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1976 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1977 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1978 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1979 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1980 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1981 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1982 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1983 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1984 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1985 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1986 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1987 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1988 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1989 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1990 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1991 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1992 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1993 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1994 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1995 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1996 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1997 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1998 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1999 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2000 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2001 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2002 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2003 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 2004 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 2005 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 2006 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 2007 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 2008 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2009 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2010 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2011 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2012 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2013 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2014 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2015 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2016 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2017 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2018 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2019 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 2020 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2031 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2032 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2033 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2034 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2035 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2036 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2037 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2038 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2039 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2040 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2041 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 2042 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2043 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2044 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2045 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2046 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2047 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2048 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2049 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2050 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2051 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2052 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2053 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2054 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2055 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2056 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2057 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2058 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2059 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2060 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2061 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2062 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2063 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2064 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2065 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2066 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2067 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2068 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 2069 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2070 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 2071 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 2072 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 2073 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 2074 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 2075 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 2076 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 2077 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 2078 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 2079 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2080 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2081 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2082 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2083 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2084 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2085 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2086 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2087 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2088 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2089 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2090 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2091 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2092 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2093 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2094 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2095 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2096 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2097 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2098 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2099 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2100 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2101 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2102 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2103 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2104 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2105 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2106 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2107 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2108 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2109 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2110 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2111 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2112 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2113 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2114 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2115 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2116 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2117 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2118 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2119 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2120 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2121 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2122 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2123 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2124 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2125 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2126 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl Compounds of Formula VII Formula VII Ex R1 R2 Y R4 R5 Z 2127 CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 2128 CH2CF3 H O CH2CF3 CF3 4-trifluoromethylphenyl 2129 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 2130 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethylphenyl 2131 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 2132 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 2133 (CH2)2 O CH2CF3 CF3 4-trifluoromethylphenyl 2134 (CH2)3 O CH2CF3 CF3 4-trifluoromethylphenyl 2135 (CH2)4 O CH2CF3 CF3 4-trifluoromethylphenyl 2136 (CH2)5 O CH2CF3 CF3 4-trifluoromethylphenyl 2137 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethylphenyl 2138 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethylphenyl 2139 CH2CH3 H O CH2CF3 CF3 4-tolyl 2140 CH2CF3 H O CH2CF3 CF3 4-tolyl 2141 CH2CH2CH3 H O CH2CF3 CF3 4-tolyl 2142 CH2CH(CH3)2 H O CH2CF3 CF3 4-tolyl 2143 cyclopropylmethyl H O CH2CF3 CF3 4-tolyl 2144 cyclobutylmethyl H O CH2CF3 CF3 4-tolyl 2145 (CH2)2 O CH2CF3 CF3 4-tolyl 2146 (CH2)3 O CH2CF3 CF3 4-tolyl 2147 (CH2)4 O CH2CF3 CF3 4-tolyl 2148 (CH2)5 O CH2CF3 CF3 4-tolyl 2149 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-tolyl 2150 Cyclopentyl H O CH2CF3 CF3 4-tolyl 2151 CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 2152 CH2CF3 H O CH2CF3 CF3 4-ethyl phenyl 2153 CH2CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 2154 CH2CH(CH3)2 H O CH2CF3 CF3 4-ethyl phenyl 2155 cyclopropylmethyl H O CH2CF3 CF3 4-ethyl phenyl 2156 cyclobutylmethyl H O CH2CF3 CF3 4-ethyl phenyl 2157 (CH2)2 O CH2CF3 CF3 4-ethyl phenyl 2158 (CH2)3 O CH2CF3 CF3 4-ethyl phenyl 2159 (CH2)4 O CH2CF3 CF3 4-ethyl phenyl 2160 (CH2)5 O CH2CF3 CF3 4-ethyl phenyl 2161 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-ethyl phenyl 2162 Cyclopentyl H O CH2CF3 CF3 4-ethyl phenyl 2163 CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 2164 CH2CF3 H O CH2CF3 CF3 4-isopropyl phenyl 2165 CH2CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 2166 CH2CH(CH3)2 H O CH2CF3 CF3 4-isopropyl phenyl 2167 cyclopropylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 2168 cyclobutylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 2169 (CH2)2 O CH2CF3 CF3 4-isopropyl phenyl 2170 (CH2)3 O CH2CF3 CF3 4-isopropyl phenyl 2171 (CH2)4 O CH2CF3 CF3 4-isopropyl phenyl 2172 (CH2)5 O CH2CF3 CF3 4-isopropyl phenyl 2173 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-isopropyl phenyl 2174 Cyclopentyl H O CH2CF3 CF3 4-isopropyl phenyl 2175 CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 2176 CH2CF3 H O CH2CF3 CF3 4-thiomethylphenyl 2177 CH2CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 2178 CH2CH(CH3)2 H O CH2CF3 CF3 4-thiomethylphenyl 2179 cyclopropylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 2180 cyclobutylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 2181 (CH2)2 O CH2CF3 CF3 4-thiomethylphenyl 2182 (CH2)3 O CH2CF3 CF3 4-thiomethylphenyl 2183 (CH2)4 O CH2CF3 CF3 4-thiomethylphenyl 2184 (CH2)5 O CH2CF3 CF3 4-thiomethylphenyl 2185 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-thiomethylphenyl 2186 Cyclopentyl H O CH2CF3 CF3 4-thiomethylphenyl 2187 CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2188 CH2CF3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2189 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2190 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2191 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2192 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2193 (CH2)2 O CH2CF3 CF3 4-trifluoromethoxyphenyl 2194 (CH2)3 O CH2CF3 CF3 4-trifluoromethoxyphenyl 2195 (CH2)4 O CH2CF3 CF3 4-trifluoromethoxyphenyl 2196 (CH2)5 O CH2CF3 CF3 4-trifluoromethoxyphenyl 2197 5,5-spiro[2.3]hexane O CH2CF3 CF3 4-trifluoromethoxyphenyl 2198 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 2199 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2200 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2201 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2202 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2203 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2204 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2205 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethylphenyl 2206 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethylphenyl 2207 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethylphenyl 2208 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethylphenyl 2209 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethylphenyl 2210 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 2211 CH2CH3 H O CH2-c-Pr CF3 4-tolyl 2212 CH2CF3 H O CH2-c-Pr CF3 4-tolyl 2213 CH2CH2CH3 H O CH2-c-Pr CF3 4-tolyl 2214 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-tolyl 2215 cyclopropylmethyl H O CH2-c-Pr CF3 4-tolyl 2216 cyclobutylmethyl H O CH2-c-Pr CF3 4-tolyl 2217 (CH2)2 O CH2-c-Pr CF3 4-tolyl 2218 (CH2)3 O CH2-c-Pr CF3 4-tolyl 2219 (CH2)4 O CH2-c-Pr CF3 4-tolyl 2220 (CH2)5 O CH2-c-Pr CF3 4-tolyl 2221 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-tolyl 2222 Cyclopentyl H O CH2-c-Pr CF3 4-tolyl 2223 CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 2224 CH2CF3 H O CH2-c-Pr CF3 4-ethyl phenyl 2225 CH2CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 2226 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-ethyl phenyl 2227 cyclopropylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 2228 cyclobutylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 2229 (CH2)2 O CH2-c-Pr CF3 4-ethyl phenyl 2230 (CH2)3 O CH2-c-Pr CF3 4-ethyl phenyl 2231 (CH2)4 O CH2-c-Pr CF3 4-ethyl phenyl 2232 (CH2)5 O CH2-c-Pr CF3 4-ethyl phenyl 2233 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-ethyl phenyl 2234 Cyclopentyl H O CH2-c-Pr CF3 4-ethyl phenyl 2235 CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 2236 CH2CF3 H O CH2-c-Pr CF3 4-isopropyl phenyl 2237 CH2CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 2238 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-isopropyl phenyl 2239 cyclopropylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 2240 cyclobutylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 2241 (CH2)2 O CH2-c-Pr CF3 4-isopropyl phenyl 2242 (CH2)3 O CH2-c-Pr CF3 4-isopropyl phenyl 2243 (CH2)4 O CH2-c-Pr CF3 4-isopropyl phenyl 2244 (CH2)5 O CH2-c-Pr CF3 4-isopropyl phenyl 2245 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-isopropyl phenyl 2246 Cyclopentyl H O CH2-c-Pr CF3 4-isopropyl phenyl 2247 CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 2248 CH2CF3 H O CH2-c-Pr CF3 4-thiomethylphenyl 2249 CH2CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 2250 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-thiomethylphenyl 2251 cyclopropylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 2252 cyclobutylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 2253 (CH2)2 O CH2-c-Pr CF3 4-thiomethylphenyl 2254 (CH2)3 O CH2-c-Pr CF3 4-thiomethylphenyl 2255 (CH2)4 O CH2-c-Pr CF3 4-thiomethylphenyl 2256 (CH2)5 O CH2-c-Pr CF3 4-thiomethylphenyl 2257 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-thiomethylphenyl 2258 Cyclopentyl H O CH2-c-Pr CF3 4-thiomethylphenyl 2259 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2260 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2261 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2262 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2263 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2264 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2265 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2266 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2267 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2268 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2269 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2270 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 2271 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2272 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2273 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2274 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2275 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2276 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2277 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2278 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2279 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2280 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2281 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2282 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 2283 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 2284 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 2285 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 2286 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 2287 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 2288 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 2289 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 2290 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 2291 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 2292 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 2293 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 2294 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 2295 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2296 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2297 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2298 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2299 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2300 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2301 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 2302 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 2303 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 2304 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 2305 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 2306 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2307 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2308 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2309 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2310 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2311 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2312 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2313 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2314 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2315 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2316 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2317 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 2318 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2319 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2320 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2321 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2322 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2323 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2324 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2325 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2326 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2327 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2328 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 2329 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 2330 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 2331 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2332 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2333 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2334 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2335 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2336 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2337 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2338 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2339 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2340 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2341 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2342 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 2343 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2344 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2345 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2346 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2347 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2348 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2349 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2350 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2351 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2352 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2353 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2354 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 2355 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2356 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 2357 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2358 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 2359 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 2360 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 2361 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 2362 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 2363 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 2364 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 2365 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 2366 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 2367 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2368 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2369 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2370 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2371 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2372 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2373 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2374 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2375 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2376 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2377 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2378 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2379 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2380 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2381 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2382 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2383 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2384 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2385 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2386 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2387 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2388 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2389 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2390 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2391 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2392 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2393 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2394 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2395 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2396 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2397 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2398 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2399 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2400 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2401 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2402 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 2403 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2404 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2405 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2406 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2407 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2408 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2409 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2410 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2411 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2412 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2413 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2414 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl Formula VII Compounds of Formula VII Ex R1 R2 Y R4 R5 Z 2415 CH2CH3 H O CH2CF3 Cl 4-trifluoro- methylphenyl 2416 CH2CF3 H O CH2CF3 Cl 4-trifluoro- methylphenyl 2417 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoro- methylphenyl 2418 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoro- methylphenyl 2419 cyclopropyl- H O CH2CF3 Cl 4-trifluoro- methyl methylphenyl 2420 cyclobutyl- H O CH2CF3 Cl 4-trifluoro- methyl methylphenyl 2421 (CH2)2 O CH2CF3 Cl 4-trifluoro- methylphenyl 2422 (CH2)3 O CH2CF3 Cl 4-trifluoro- methylphenyl 2423 (CH2)4 O CH2CF3 Cl 4-trifluoro- methylphenyl 2424 (CH2)5 O CH2CF3 Cl 4-trifluoro- methylphenyl 2425 5,5-spiro[2.3] O CH2CF3 Cl 4-trifluoro- hexane methylphenyl 2426 Cyclopentyl H O CH2CF3 Cl 4-trifluoro- methylphenyl 2427 CH2CH3 H O CH2CF3 Cl 4-tolyl 2428 CH2CF3 H O CH2CF3 Cl 4-tolyl 2429 CH2CH2CH3 H O CH2CF3 Cl 4-tolyl 2430 CH2CH(CH3)2 H O CH2CF3 Cl 4-tolyl 2431 cyclopropyl- H O CH2CF3 Cl 4-tolyl methyl 2432 cyclobutyl- H O CH2CF3 Cl 4-tolyl methyl 2433 (CH2)2 O CH2CF3 Cl 4-tolyl 2434 (CH2)3 O CH2CF3 Cl 4-tolyl 2435 (CH2)4 O CH2CF3 Cl 4-tolyl 2436 (CH2)5 O CH2CF3 Cl 4-tolyl 2437 5,5-spiro[2.3] O CH2CF3 Cl 4-tolyl hexane 2438 Cyclopentyl H O CH2CF3 Cl 4-tolyl 2439 CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 2440 CH2CF3 H O CH2CF3 Cl 4-ethyl phenyl 2441 CH2CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 2442 CH2CH(CH3)2 H O CH2CF3 Cl 4-ethyl phenyl 2443 cyclopropyl- H O CH2CF3 Cl 4-ethyl phenyl methyl 2444 cyclobutyl- H O CH2CF3 Cl 4-ethyl phenyl methyl 2445 (CH2)2 O CH2CF3 Cl 4-ethyl phenyl 2446 (CH2)3 O CH2CF3 Cl 4-ethyl phenyl 2447 (CH2)4 O CH2CF3 Cl 4-ethyl phenyl 2448 (CH2)5 O CH2CF3 Cl 4-ethyl phenyl 2449 5,5-spiro[2.3] O CH2CF3 Cl 4-ethyl phenyl hexane 2450 Cyclopentyl H O CH2CF3 Cl 4-ethyl phenyl 2451 CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 2452 CH2CF3 H O CH2CF3 Cl 4-isopropyl phenyl 2453 CH2CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 2454 CH2CH(CH3)2 H O CH2CF3 Cl 4-isopropyl phenyl 2455 cyclopropyl- H O CH2CF3 Cl 4-isopropyl methyl phenyl 2456 cyclobutyl- H O CH2CF3 Cl 4-isopropyl methyl phenyl 2457 (CH2)2 O CH2CF3 Cl 4-isopropyl phenyl 2458 (CH2)3 O CH2CF3 Cl 4-isopropyl phenyl 2459 (CH2)4 O CH2CF3 Cl 4-isopropyl phenyl 2460 (CH2)5 O CH2CF3 Cl 4-isopropyl phenyl 2461 5,5-spiro[2.3] O CH2CF3 Cl 4-isopropyl hexane phenyl 2462 Cyclopentyl H O CH2CF3 Cl 4-isopropyl phenyl 2463 CH2CH3 H O CH2CF3 Cl 4-thiomethyl- phenyl 2464 CH2CF3 H O CH2CF3 Cl 4-thiomethyl- phenyl 2465 CH2CH2CH3 H O CH2CF3 Cl 4-thiomethyl- phenyl 2466 CH2CH(CH3)2 H O CH2CF3 Cl 4-thiomethyl- phenyl 2467 cyclopropyl- H O CH2CF3 Cl 4-thiomethyl- methyl phenyl 2468 cyclobutyl- H O CH2CF3 Cl 4-thiomethyl- methyl phenyl 2469 (CH2)2 O CH2CF3 Cl 4-thiomethyl- phenyl 2470 (CH2)3 O CH2CF3 Cl 4-thiomethyl- phenyl 2471 (CH2)4 O CH2CF3 Cl 4-thiomethyl- phenyl 2472 (CH2)5 O CH2CF3 Cl 4-thiomethyl- phenyl 2473 5,5-spiro[2.3] O CH2CF3 Cl 4-thiomethyl- hexane phenyl 2474 Cyclopentyl H O CH2CF3 Cl 4-thiomethyl- phenyl 2475 CH2CH3 H O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2476 CH2CF3 H O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2477 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2478 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2479 cyclopropyl- H O CH2CF3 Cl 4-trifluoro- methyl methoxyphenyl 2480 cyclobutyl- H O CH2CF3 Cl 4-trifluoro- methyl methoxyphenyl 2481 (CH2)2 O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2482 (CH2)3 O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2483 (CH2)4 O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2484 (CH2)5 O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2485 5,5-spiro[2.3] O CH2CF3 Cl 4-trifluoro- hexane methoxyphenyl 2486 Cyclopentyl H O CH2CF3 Cl 4-trifluoro- methoxyphenyl 2487 CH2CH3 H O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2488 CH2CF3 H O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2489 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2490 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2491 cyclopropyl- H O CH2-c-Pr Cl 4-trifluoro- methyl methylphenyl 2492 cyclobutyl- H O CH2-c-Pr Cl 4-trifluoro- methyl methylphenyl 2493 (CH2)2 O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2494 (CH2)3 O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2495 (CH2)4 O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2496 (CH2)5 O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2497 5,5-spiro[2.3] O CH2-c-Pr Cl 4-trifluoro- hexane methylphenyl 2498 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoro- methylphenyl 2499 CH2CH3 H O CH2-c-Pr Cl 4-tolyl 2500 CH2CF3 H O CH2-c-Pr Cl 4-tolyl 2501 CH2CH2CH3 H O CH2-c-Pr Cl 4-tolyl 2502 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-tolyl 2503 cyclopropyl- H O CH2-c-Pr Cl 4-tolyl methyl 2504 cyclobutyl- H O CH2-c-Pr Cl 4-tolyl methyl 2505 (CH2)2 O CH2-c-Pr Cl 4-tolyl 2506 (CH2)3 O CH2-c-Pr Cl 4-tolyl 2507 (CH2)4 O CH2-c-Pr Cl 4-tolyl 2508 (CH2)5 O CH2-c-Pr Cl 4-tolyl 2509 5,5-spiro[2.3] O CH2-c-Pr Cl 4-tolyl hexane 2510 Cyclopentyl H O CH2-c-Pr Cl 4-tolyl 2511 CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 2512 CH2CF3 H O CH2-c-Pr Cl 4-ethyl phenyl 2513 CH2CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 2514 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-ethyl phenyl 2515 cyclopropyl- H O CH2-c-Pr Cl 4-ethyl phenyl methyl 2516 cyclobutyl- H O CH2-c-Pr Cl 4-ethyl phenyl methyl 2517 (CH2)2 O CH2-c-Pr Cl 4-ethyl phenyl 2518 (CH2)3 O CH2-c-Pr Cl 4-ethyl phenyl 2519 (CH2)4 O CH2-c-Pr Cl 4-ethyl phenyl 2520 (CH2)5 O CH2-c-Pr Cl 4-ethyl phenyl 2521 5,5-spiro[2.3] O CH2-c-Pr Cl 4-ethyl phenyl hexane 2522 Cyclopentyl H O CH2-c-Pr Cl 4-ethyl phenyl 2523 CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 2524 CH2CF3 H O CH2-c-Pr Cl 4-isopropyl phenyl 2525 CH2CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 2526 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-isopropyl phenyl 2527 cyclopropyl- H O CH2-c-Pr Cl 4-isopropyl methyl phenyl 2528 cyclobutyl- H O CH2-c-Pr Cl 4-isopropyl methyl phenyl 2529 (CH2)2 O CH2-c-Pr Cl 4-isopropyl phenyl 2530 (CH2)3 O CH2-c-Pr Cl 4-isopropyl phenyl 2531 (CH2)4 O CH2-c-Pr Cl 4-isopropyl phenyl 2532 (CH2)5 O CH2-c-Pr Cl 4-isopropyl phenyl 2533 5,5-spiro[2.3] O CH2-c-Pr Cl 4-isopropyl hexane phenyl 2534 Cyclopentyl H O CH2-c-Pr Cl 4-isopropyl phenyl 2535 CH2CH3 H O CH2-c-Pr Cl 4-thiomethyl- phenyl 2536 CH2CF3 H O CH2-c-Pr Cl 4-thiomethyl- phenyl 2537 CH2CH2CH3 H O CH2-c-Pr Cl 4-thiomethyl- phenyl 2538 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-thiomethyl- phenyl 2539 cyclopropyl- H O CH2-c-Pr Cl 4-thiomethyl- methyl phenyl 2540 cyclobutyl- H O CH2-c-Pr Cl 4-thiomethyl- methyl phenyl 2541 (CH2)2 O CH2-c-Pr Cl 4-thiomethyl- phenyl 2542 (CH2)3 O CH2-c-Pr Cl 4-thiomethyl- phenyl 2543 (CH2)4 O CH2-c-Pr Cl 4-thiomethyl- phenyl 2544 (CH2)5 O CH2-c-Pr Cl 4-thiomethyl- phenyl 2545 5,5-spiro[2.3] O CH2-c-Pr Cl 4-thiomethyl- hexane phenyl 2546 Cyclopentyl H O CH2-c-Pr Cl 4-thiomethyl- phenyl 2547 CH2CH3 H O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2548 CH2CF3 H O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2549 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2550 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2551 cyclopropyl- H O CH2-c-Pr Cl 4-trifluoro- methyl methoxyphenyl 2552 cyclobutyl- H O CH2-c-Pr Cl 4-trifluoro- methyl methoxyphenyl 2553 (CH2)2 O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2554 (CH2)3 O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2555 (CH2)4 O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2556 (CH2)5 O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2557 5,5-spiro[2.3] O CH2-c-Pr Cl 4-trifluoro- hexane methoxyphenyl 2558 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoro- methoxyphenyl 2559 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2560 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2561 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2562 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2563 cyclopropyl- H O CH2CF3 OCH2CF3 4-trifluoro- methyl methylphenyl 2564 cyclobutyl- H O CH2CF3 OCH2CF3 4-trifluoro- methyl methylphenyl 2565 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2566 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2567 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2568 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2569 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-trifluoro- hexane methylphenyl 2570 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoro- methylphenyl 2571 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 2572 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 2573 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 2574 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 2575 cyclopropyl- H O CH2CF3 OCH2CF3 4-tolyl methyl 2576 cyclobutyl- H O CH2CF3 OCH2CF3 4-tolyl methyl 2577 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 2578 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 2579 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 2580 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 2581 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-tolyl hexane 2582 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 2583 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2584 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2585 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2586 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 2587 cyclopropyl- H O CH2CF3 OCH2CF3 4-ethyl phenyl methyl 2588 cyclobutyl- H O CH2CF3 OCH2CF3 4-ethyl phenyl methyl 2589 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 2590 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 2591 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 2592 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 2593 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-ethyl phenyl hexane 2594 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 2595 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2596 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2597 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2598 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2599 cyclopropyl- H O CH2CF3 OCH2CF3 4-isopropyl methyl phenyl 2600 cyclobutyl- H O CH2CF3 OCH2CF3 4-isopropyl methyl phenyl 2601 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2602 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2603 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2604 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 2605 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-isopropyl hexane phenyl 2606 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 2607 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2608 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2609 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2610 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2611 cyclopropyl- H O CH2CF3 OCH2CF3 4-thiomethyl- methyl phenyl 2612 cyclobutyl- H O CH2CF3 OCH2CF3 4-thiomethyl- methyl phenyl 2613 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2614 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2615 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2616 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2617 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-thiomethyl- hexane phenyl 2618 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethyl- phenyl 2619 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2620 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2621 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2622 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2623 cyclopropyl- H O CH2CF3 OCH2CF3 4-trifluoro- methyl methoxyphenyl 2624 cyclobutyl- H O CH2CF3 OCH2CF3 4-trifluoro- methyl methoxyphenyl 2625 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2626 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2627 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2628 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2629 5,5-spiro[2.3] O CH2CF3 OCH2CF3 4-trifluoro- hexane methoxyphenyl 2630 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoro- methoxyphenyl 2632 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2633 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2634 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2635 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2636 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-trifluoro- methyl methylphenyl 2637 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-trifluoro- methyl methylphenyl 2638 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2639 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2640 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2641 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2642 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-trifluoro- hexane methylphenyl 2643 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoro- methylphenyl 2644 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2645 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 2646 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 2647 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 2648 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-tolyl methyl 2649 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-tolyl methyl 2650 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 2651 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 2652 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 2653 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 2654 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-tolyl hexane 2655 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 2656 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2657 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2658 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2659 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2660 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-ethyl phenyl methyl 2661 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-ethyl phenyl methyl 2662 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2663 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2664 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2665 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2666 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-ethyl phenyl hexane 2667 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 2668 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2669 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2670 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2671 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2672 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-isopropyl methyl phenyl 2673 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-isopropyl methyl phenyl 2674 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2675 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2676 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2677 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2678 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-isopropyl hexane phenyl 2679 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 2680 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2681 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2682 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2683 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2684 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-thiomethyl- methyl phenyl 2685 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-thiomethyl- methyl phenyl 2686 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2687 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2688 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2689 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2690 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-thiomethyl- hexane phenyl 2691 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethyl- phenyl 2692 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2693 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2694 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2695 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2696 cyclopropyl- H O CH2-c-Pr OCH2CF3 4-trifluoro- methyl methoxyphenyl 2697 cyclobutyl- H O CH2-c-Pr OCH2CF3 4-trifluoro- methyl methoxyphenyl 2698 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2699 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2700 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2701 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl 2702 5,5-spiro[2.3] O CH2-c-Pr OCH2CF3 4-trifluoro- hexane methoxyphenyl 2703 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoro- methoxyphenyl Formula III Compounds of Formula III Ex R1 R2 Y R4 R5 Z 2704 CH2CH3 H O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2705 CH2CF3 H O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2706 CH2CH2CH3 H O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2707 CH2CH(CH3)2 H O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2708 cyclopropyl- H O CH2CH2CF3 Cl 4-trifluoromethyl- methyl phenyl 2709 cyclobutyl- H O CH2CH2CF3 Cl 4-trifluoromethyl- methyl phenyl 2710 (CH2)2 O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2711 (CH2)3 O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2712 (CH2)4 O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2713 (CH2)5 O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl 2714 5,5-spiro[2.3] O CH2CH2CF3 Cl 4-trifluoromethyl- hexane phenyl 2715 Cyclopentyl H O CH2CH2CF3 Cl 4-trifluoromethyl- phenyl Formula III Compounds of Formula III Ex R1 R2 Y R4 R5 Z 2716 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2717 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2718 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2719 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2720 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2721 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2722 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2723 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2724 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2725 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2726 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2727 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2733 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2735 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2737 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2738 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2739 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2745 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2747 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2749 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2750 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2751 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2752 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2753 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2754 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2755 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2756 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2757 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2758 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2759 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2760 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2761 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2762 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2763 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2769 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2771 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2773 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2774 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2775 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2781 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2783 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2785 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2786 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2787 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2788 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2789 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2790 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2791 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2792 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2793 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2794 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2795 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2796 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2797 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2798 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2799 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2805 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2807 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2809 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2810 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2811 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2817 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2819 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2821 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2822 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2823 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2824 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2825 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2826 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2827 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2828 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2829 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2830 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2831 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2832 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2833 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2834 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2835 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2841 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2843 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2845 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2846 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2847 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2853 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2855 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2857 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2858 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2859 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole Formula IV Compounds of Formula IV Ex R1 R2 X R3 R5 Z 2860 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2861 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2862 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2863 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2864 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2865 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2866 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2867 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2868 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2869 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2870 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2871 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 2872 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2873 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2874 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2875 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2876 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2877 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2878 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2879 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2880 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2881 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2882 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2883 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 2884 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2885 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2886 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2887 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2888 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2889 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2890 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2891 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2892 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2893 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2894 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2895 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 2896 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2897 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2898 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2899 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2900 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2901 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2902 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2903 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2904 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2905 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2906 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2907 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 2908 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2909 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2910 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2911 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2912 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2913 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2914 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2915 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2916 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2917 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2918 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2919 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 2920 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2921 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2922 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2923 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2924 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2925 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2926 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2927 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2928 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2929 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2930 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2931 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 2932 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2933 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2934 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2935 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2936 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2937 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2938 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2939 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2940 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2941 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2942 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2943 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 2944 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2945 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2946 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2947 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2948 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2949 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2950 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2951 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2952 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2953 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2954 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2955 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 2956 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2957 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2958 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2959 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2960 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2961 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2962 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2963 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2964 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2965 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2966 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2967 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 2968 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2969 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2970 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2971 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2972 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2973 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2974 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2975 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2976 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2977 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2978 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2979 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 2980 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2981 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2982 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2983 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2984 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2985 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2986 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2987 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2988 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2989 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2990 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2991 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 2992 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2993 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2994 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2995 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2996 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2997 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2998 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 2999 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3000 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3001 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3002 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3003 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole Formula VII Compounds of Formula VII Ex R1 R2 Y R4 R5 Z 3004 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3005 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3006 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3007 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3008 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3009 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3010 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3011 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3012 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3013 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3014 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3015 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] oxadiazole 3016 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3017 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3018 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3019 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3020 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3021 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3022 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3023 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3024 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3025 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3026 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3027 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] oxadiazole 3028 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3029 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3030 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3031 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3032 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3033 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3034 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3035 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3036 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3037 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3038 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3039 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] oxadiazole 3040 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3041 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3042 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3043 CH2CH(CH3)2 H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3044 cyclopropylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3045 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3046 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3047 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3048 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3049 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3050 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3051 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5] thiadiazole 3052 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3053 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3054 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3055 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3056 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3057 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3058 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3059 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3060 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3061 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3062 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3063 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5] thiadiazole 3064 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3065 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3066 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3067 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3068 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3069 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3070 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3071 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3072 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3073 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3074 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3075 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5] thiadiazole 3076 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3077 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3078 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3079 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3080 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3081 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3082 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3083 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3084 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3085 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3086 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3087 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] oxadiazole 3088 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3089 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3090 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3091 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3092 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3093 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3094 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3095 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3096 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3097 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3098 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3099 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] oxadiazole 3100 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3101 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3102 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3103 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3104 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3105 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3106 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3107 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3108 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3109 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3110 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3111 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] oxadiazole 3112 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3113 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3114 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3115 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3116 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3117 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3118 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3119 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3120 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3121 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3122 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3123 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5] thiadiazole 3124 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3125 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3126 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3127 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3128 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3129 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3130 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3131 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3132 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3133 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3134 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3135 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5] thiadiazole 3136 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3137 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3138 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3139 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3140 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3141 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3142 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3143 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3144 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3145 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3146 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole 3147 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5] thiadiazole EXPERIMENTAL PROCEDURES
Example 534
2-(6-cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step-1:
2-(3-Bromo-4-hydroxyphenyl)-4-methylpentanoate
Step-2:
2-(3-Bromo-4-hydroxy-5-nitrophenyl)-4-methylpentanoic acid
Step 3
Ethyl 2-(3-bromo-4-(cyclopropylmethoxy)-5-nitrophenyl)-4-methylpentanoate
Step 4
Ethyl 2-(6-(cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 5
2-(6-(Cyclopropylmethoxy)-5-nitro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 554
2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(5-amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 3
2-(5-Amino-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 484
2-(6-cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(6-cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 2
2-(6-Cyclopropylmethoxy)-5-chloro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 264
2-(6-cyclopropylmethoxy)-5-fluoro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(6-cyclopropylmethoxy)-5-amino-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 2
2-(6-cyclopropylmethoxy)-5-fluoro-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 724
2-(2-cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid
Step 1
Diethyl 2-(2,5-difluoro-4-nitrophenyl)-2-isobutylmalonate
Step 2
2-(2,5-Difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid
Step 3
2-(2,5-Difluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 4
2-(5-cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 5
2-(5-Cyclopropylmethoxy-2-fluoro-4-amino-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 6
2-(5-Cyclopropylmethoxy-2-fluoro-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 7
2-(2-Cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 8
2-(2-Cyclopropylmethoxy-5-fluoro-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid
Example 485
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl 2-(3-bromo-4-hydroxyphenyl)acetate
Step 2
Ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate
Step 3
Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate
Step 4
Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate
Step 5
Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 6
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 414
2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-amino-5-bromo-4-hydroxyphenyl)-4-methylpentanoate
Step 2
Ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)-4-methylpentanoate
Step 3
Ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-4-methyl pentanoate
Step 4
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 5
2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 2
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methyl pentanoic acid
Example 1055
2-(6-Cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic Acid
Step 1
Diethyl 2-isobutyl-2-(4-nitro-3-(trifluoromethyl)phenyl)malonate
Step 2
4-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid
Step 3
4-Methyl-2-(4-nitro-3-trifluoromethyl-phenyl)-pentanoic acid ethyl ester
Step 4
2-(4-Amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 5
2-(4-Hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 6
2-(4-Cyclopropylmethoxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 7
2-(3-Amino-4-cyclopropylmethoxy-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 8
2-(4-Cyclopropylmethoxy-3-iodo-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 9
2-(6-Cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid ethyl ester
Step 10
2-(6-Cyclopropylmethoxy-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-4-methyl-pentanoic acid
Example 754
2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-5-(cyclopropylmethoxy)-2-fluorophenyl)-4-methylpentanoic acid
Step 1.
Cyclopropylmethyl 2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-5-(cyclopropylmethoxy)-2-fluorophenyl)-4-methylpentanoate
Step 2
2-(4-benzo[1,2,5]oxadiazol-5-yl-5-cyclopropylmethoxy-2-fluoro-phenyl)-4-methylpentanoic acid
Example 2959
2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid
Step 1
2-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid diethyl ester
Step 2
2-(3-fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid
Step 3
2-(3-Fluoro-4-nitro-phenyl)-4-methyl-pentanoic acid ethyl ester
Step 4
2-(3-Cyclopropylmethoxy-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 5
2-(4-Amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 6
2-(4-Amino-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 7
2-(3-Chloro-5-cyclopropylmethoxy-4-iodo-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 8
2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 9
2-(4-benzo[1,2,5]oxadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid
Example 2995
2-(4-Benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid
Step 1
2-(4-Benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 2
2-(4-Benzo[1,2,5]thiadiazol-5-yl-3-chloro-5-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid
Example 1904
2-(2-Chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid
Step 1
2-(2-Chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 2
2-(2-Chloro-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-4-yl)-4-methyl-pentanoic acid
Example 3200
2-(2,4′-Dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid
Step 1
2-(2,4′-Dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid cyclopropylmethyl ester
Step 2
2-(2,4′-Dichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-4-methyl-pentanoic acid
Example 3201
4-Methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid
Step 1
4-Methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid cyclopropylmethyl ester
Step 2
4-Methyl-2-(2,3′,4′-trichloro-6-cyclopropylmethoxy-biphenyl-4-yl)-pentanoic acid
Example 1976
2-[2,6-Bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-4-methyl-pentanoic acid
Step 1
5-Fluoro-2-nitro-1,3-bis-(2,2,2-trifluoro-ethoxy)-benzene
Step 2
2-[4-Nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-malonic acid diethyl ester
Step 3
[4-Nitro-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]acetic acid ethyl ester
Step 4
[4-Amino-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]acetic acid ethyl ester
Step 5
[4-Iodo-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]acetic acid ethyl ester
Step 6
[2,6-Bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-acetic acid ethyl ester
Step 7
2-[2,6-Bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-4-methyl-pentanoic acid
Example 2420
2-[6-Chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid
Step 1
4-Fluoro-1-nitro-2-(2,2,2-trifluoro-ethoxy)-benzene
Step 2
[4-Nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]acetic acid
Step 3
[4-Nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]acetic acid methyl ester
Step 4
3-Cyclobutyl-2-[4-nitro-3-(2,2,2-trifluoro-ethoxy)-phenyl]-propionic acid methyl ester
Step 5
2-[4-Amino-3-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester
Step 6
2-[4-Amino-3-bromo-5-(2,2,2-trifluoro-ethoxy)-phenyl]-3-cyclobutyl-propionic acid methyl ester
Step 7
2-[6-Amino-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester
Step 8
2-[6-Chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid methyl ester
Step 9
2-[6-Chloro-5-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-3-yl]-3-cyclobutyl-propionic acid
Example 415
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl 2-(3-chloro-4-hydroxyphenyl)acetate
Step 2
Ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate
Step 3
Ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-acetate
Step 4
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)acetate
Step 5
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 6
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 1269
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acid
Step 1
Ethyl-1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(Trifluoromethyl)biphenyl-3-yl)-cyclo butane carboxylate
Step 2
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclobutane carboxylic acid
Example 419
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclopentane carboxylic acid
Step 1
Ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclo pentane carboxylate
Step 2
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclopentane carboxylic acid
Example 3202
4-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylic acid
Step 1
Ethyl 4-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylate
Step 2
4-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)tetrahydro-2H-pyran-4-carboxylic acid
Example 3203
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylic acid
Step 1
Ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylate
Step 2
1-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4-dimethylcyclohexanecarboxylic acid
Example 1270
1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexane carboxylic acid
Step 1
Ethyl 1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexanecarboxylate
Step 2
1-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-cyclohexane carboxylic acid
Example 1271
5-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-spiro[2,3]hexane-5-carboxylic acid
Step 1
Ethyl 5-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-Spiro[2,3]hexane-5-carboxylate
Step 2
5-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-spiro[2,3]hexane-5-carboxylic acid
Example 1268
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoic acid
Step 1
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoate
Step 2
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoic acid
Example 1272
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetic acid
Step 1
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetate
Step 2
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-2-cyclopentylacetic acid
Example 3204
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoic acid
Step 1
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoate
Step 2
2-(5-Chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-(4-fluorophenyl)propanoic acid
Example 1905
2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropylpropanoic acid
Step 1
2-(Cyclopropylmethoxy)-4-fluoro-1-nitrobenzene
Step 2
Diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate
Step 3
2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetic acid
Step 4
Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate
Step 5
Ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)acetate
Step 6
Ethyl 2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)acetate
Step 7
Ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate
Step 8
Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate
Step 9
2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropylpropanoic acid
Example 1908
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-cyclobutanecarboxylic acid
Example 1909
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-cyclopentanecarboxylic acid
Example 2491
2-(6-Chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl 3-cyclopropyl-2-(3(cyclopropylmethoxy)-4-nitrophenyl)propanoate
Step 2
Ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-3-cyclopropylpropanoate
Step 3
Ethyl 2-(4-amino-3-bromo-5-(Cyclopropylmethoxy)phenyl)-3-cyclopropyl propanoate
Step 4
Ethyl 2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 5
Ethyl 2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 6
2-(6-Chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 2494
1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid
Step 1
Ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclobutanecarboxylate
Step 2
Ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate
Step 3
Ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclobutanecarboxylate
Step 4
Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate
Step 5
Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate
Step 6
1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid
Example 2495
1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylic acid
Step 1
Ethyl 1-(3-(cyclopropylmethoxy)-4-nitrophenyl)cyclopentanecarboxylate
Step 2
Ethyl 1-(4-amino-3-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate
Step 3
Ethyl 1-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)cyclopentanecarboxylate
Step 4
Ethyl 1-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate
Step 5
Ethyl 1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate
Step 6
1-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylic acid
Example 2419
2-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl 3-cyclopropyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)propanoate
Step 2
Ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate
Step 3
Ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate
Step 4
Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 5
Ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 6
2-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 2422
Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate
Step 1
Ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 2
Ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 3
Ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 4
Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate
Step 5
Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylate
Step 6
1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclobutanecarboxylic acid
Example 2423
1-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylic acid
Step 1
Ethyl 1-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate
Step 2
Ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate
Step 3
Ethyl 1-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate
Step 4
Ethyl 1-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate
Step 5
Ethyl 1-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylate
Step 6
1-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)cyclopentanecarboxylic acid
Example 2418
2-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 4-methyl-2-(4-nitro-3-(2,2,2-trifluoroethoxy)phenyl)pentanoate
Step 2
Ethyl 2-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate
Step 3
Ethyl 2-(4-amino-3-bromo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate
Step 4
Ethyl 2-(6-amino-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 5
Ethyl 2-(6-chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 6
2-(6-Chloro-5-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 1277
2-(5-Chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Step 1
Ethyl 2-(3-chloro-4-hydroxyphenyl)acetate
Step 2
Ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate
Step 3
Ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)acetate
Step 4
Ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate
Step 5
Ethyl 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoate
Step 7
2-(5-Chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 1289
2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl 2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate
Step 2
2-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropylpropanoic acid
Example 1313
2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Step 1
Ethyl 2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate
Step 2
2-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Example 1325
2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Step 1
Ethyl 2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate
Step 2
2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Example 1301
2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Step 1
Ethyl 2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoate
Step 2
2-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)-3-cyclopropyl propanoic acid
Example 1280
1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Step 1
Ethyl 1-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 2
Ethyl 1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutanecarboxylate
Step 3
1-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Step 4
Ethyl 1-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate
Step 5
1-(5-chloro-4′-ethyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Example 1316
1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Step 1
Ethyl 1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate
Step 2
1-(5-chloro-4′-(methylthio)-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Example 1304
1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Step 1
Ethyl 1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylate
Step 2
1-(5-chloro-4′-isopropyl-6-(2,2,2-trifluoroethoxy)biphenyl-3-yl)cyclobutane carboxylic acid
Example 1833
2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropylpropanoic acid
Step 1
Ethyl-2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropyl propanoate
Step 2
Ethyl 2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate
Step 3
Ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropyl propanoate
Step 4
2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-3-cyclopropylpropanoic acid
Example 1836
1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutane carboxylic acid
Step 1
Ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 2
Ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate
Step 3
Ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutanecarboxylate
Step 4
1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutanecarboxylic acid
Example 1837
Ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentanecarboxylate
Step 1
Ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate
Step 2
Ethyl 1-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)cyclopentanecarboxylate
Step 3
Ethyl-1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentanecarboxylate
Step 4
1-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentanecarboxylic acid
Example 1832
2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate
Step 2
Ethyl-2-(3-chloro-4-iodo-5-(2,2,2-trifluoroethoxy)phenyl)-4-methylpentanoate
Step 3
Ethyl-2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoate
Step 4
2-(2-chloro-6-(2,2,2-trifluoroethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)-4-methylpentanoic acid
Example 1908
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutane carboxylic acid
2-(Cyclopropylmethoxy)-4-fluoro-1-nitrobenzene
Step 2
Diethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)malonate
Step 3
Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)acetate
Step 4
Ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)acetate
Step 5
Ethyl 2-(4-amino-3-chloro-5-(cyclopropylmethoxy)phenyl)acetate
Step 6
Ethyl 2-(3-chloro-5-(cyclopropylmethoxy)-4-iodophenyl)acetate
Step 7
Ethyl 2-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)acetate
Step 8
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclobutane carboxylic acid
Example 1909
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentane carboxylic acid
1-(2-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-4-yl)cyclopentane carboxylic acid
Example 2418
2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-(cyclopropylmethoxy)-4-nitrophenyl)-4-methylpentanoate
Step 2
Ethyl 2-(4-amino-3-(cyclopropylmethoxy)phenyl)-4-methylpentanoate
Step 3
Ethyl 2-(4-amino-3-bromo-5-(cyclopropylmethoxy)phenyl)-4-methylpentanoate
Step 4
Ethyl-2-(6-amino-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 5
Ethyl-2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 6
2-(6-chloro-5-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3205
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoic acid
Step 1
Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)acetate
Step 2
Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methoxybutanoate
Step 3
Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoate
Step 4
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoic acid
Example 3206
2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methyl pentanoate
Step 2
Ethyl 2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate
Step 3
2-(3-(benzo[d]thiazol-6-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Example 514
2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate
2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Example 524
2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoate
Step 2
2-(3-(benzo[c][1,2,5]thiadiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Example 3207
2-(6-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(3-bromo-5-(chlorosulfonyl)-4-hydroxyphenyl)-4-methyl pentanoate
Step 2
Ethyl 2-(3-bromo-5-(N,N-dimethylsulfamoyl)-4-hydroxyphenyl)-4-methylpentanoate
Step 3
Ethyl 2-(3-bromo-4-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)phenyl)-4-methylpentanoate
Step 4
2-(6-(cyclopropylmethoxy)-5-(N,N-dimethylsulfamoyl)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 5
Ethyl 2-(6-(cyclopropylmethoxy)-5-iodo-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Example 3210
2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 2
2-(5-cyano-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3208
2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Step 1
Ethyl 2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoate
Step 2
2-(6-(cyclopropylmethoxy)-5-(methylthio)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3209
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-methylbutanoic acid
Step 1
Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)phenyl)-3-methylbutanoate
Step 2
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-methylbutanoic acid
Example 482
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid
Step 1
Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoate
Step 2
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4,4,4-trifluorobutanoic acid
Example 3211
2-(5-chloro-6-(cyclopropylmethoxy)biphenyl-3-yl)-4-methylpentanoic acid
Example 3212
2-(5-chloro-6-(2-methoxyethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3213
2-(5-chloro-6-(cyclopropylmethoxy)-3′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3214
2-(5-bromo-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methylpentanoic acid
Example 3215
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-methylpentanoic acid
Example 3216
2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-3-phenylpropanoic acid
Example 3217
2-(3-(benzo[d]thiazol-5-yl)-5-chloro-4-(cyclopropylmethoxy)phenyl)-4-methylpentanoic acid
Pharmacology Experimental
Measurement of Aβ In Vitro
B indicates a compound has an EC50 for lowering Aβ42 of >1 μM but <5 μM
C indicates a compound has an EC50 for lowering Aβ42 of >5 μM
264 A 414 A 415 A 419 A 464 A 474 A 480 A 481 A 482 A 483 A 484 A 485 A 488 A 489 A 494 A 504 A 514 A 524 A 534 A 554 A 724 A 754 B 1055 A 1268 A 1269 A 1270 A 1271 A 1272 A 1277 A 1280 A 1289 A 1292 A 1301 A 1304 A 1313 A 1316 A 1325 A 1334 A 1832 A 1833 A 1836 A 1837 A 1904 A 1905 A 1908 A 1909 A 1976 A 2418 A 2419 A 2422 A 2423 A 2490 A 2491 A 2494 A 2495 A 2708 A 2959 A 2995 A 3200 A 3201 A 3202 B 3203 A 3204 A 3205 A 3206 A 3207 B 3208 A 3209 A 3210 A 3211 A 3212 A 3213 A 3214 A 3215 A 3216 A 3217 B 484 2-(5-chloro-6-(cyclopropylmethoxy)-4′- 0.069 (trifluoromethyl)biphenyl-3-yl)-4- methylpentanoic acid 514 2-(3-(benzo[c][1,2,5]oxadiazol-5-yl)-5-chloro-4- 0.274 (cyclopropylmethoxy)phenyl)-4-methylpentanoic acid 2959 2-(4-(benzo[c][1,2,5]oxadiazol-5-yl)-3-chloro-5- 0.298 (2-cyclopropylethyl)phenyl)-4-methylpentanoic acid 2995 2-(4-(benzo[c][1,2,5]thiadiazol-5-yl)-3-chloro-5- 0.220 (2-cyclopropylethyl)phenyl)-4-methylpentanoic acid 3210 2-(5-cyano-6-(cyclopropylmethoxy)-4′- 0.275 (trifluoromethyl)biphenyl-3-yl)-4- methylpentanoic acid Experimental Procedures for Rat Primary Cortical Culture-Based Abeta1
Measurement of Aβ 42 In Vivo
In Vivo Studies (Rats)
Analysis of In Vivo Aβ Lowering Studies
Pharmacokinetic Analysis
Sample Preparation
LC-MS/MS Analysis
Glucuronidation Protocols
Pharmacology
Dosage and Administration
Example R1 R2 Y R4 R5 Z 100 CH3 H O CH2CH3 F 4-fluorophenyl 101 CH2CH3 H O CH2CH3 F 4-fluorophenyl 102 CH2CH3 H O CH2CH3 F 4-fluorophenyl 103 CH2CH2CH3 H O CH2CH3 F 4-fluorophenyl 104 CH2CH(CH3)2 H O CH2CH3 F 4-fluorophenyl 105 cyclopropylmethyl H O CH2CH3 F 4-fluorophenyl 106 SCH(CH3)2 H O CH2CH3 F 4-fluorophenyl 107 OCH2CH3 H O CH2CH3 F 4-fluorophenyl 108 (CH2)2 O CH2CH3 F 4-fluorophenyl 109 (CH2)4 O CH2CH3 F 4-fluorophenyl 110 CH3 H O CH2CH3 F 4-chlorophenyl 111 CH2CH3 H O CH2CH3 F 4-chlorophenyl 112 CH2CH3 H O CH2CH3 F 4-chlorophenyl 113 CH2CH2CH3 H O CH2CH3 F 4-chlorophenyl 114 CH2CH(CH3)2 H O CH2CH3 F 4-chlorophenyl 115 cyclopropylmethyl H O CH2CH3 F 4-chlorophenyl 116 SCH(CH3)2 H O CH2CH3 F 4-chlorophenyl 117 OCH2CH3 H O CH2CH3 F 4-chlorophenyl 118 (CH2)2 O CH2CH3 F 4-chlorophenyl 119 (CH2)4 O CH2CH3 F 4-chlorophenyl 120 CH3 H O CH2CH3 F 4-trifluoromethylphenyl 121 CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 122 CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 123 CH2CH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 124 CH2CH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 125 cyclopropylmethyl H O CH2CH3 F 4-trifluoromethylphenyl 126 SCH(CH3)2 H O CH2CH3 F 4-trifluoromethylphenyl 127 OCH2CH3 H O CH2CH3 F 4-trifluoromethylphenyl 128 (CH2)2 O CH2CH3 F 4-trifluoromethylphenyl 129 (CH2)4 O CH2CH3 F 4-trifluoromethylphenyl 130 CH3 H O CH2CH3 F 4-methoxyphenyl 131 CH2CH3 H O CH2CH3 F 4-methoxyphenyl 132 CH2CH3 H O CH2CH3 F 4-methoxyphenyl 133 CH2CH2CH3 H O CH2CH3 F 4-methoxyphenyl 134 CH2CH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 135 cyclopropylmethyl H O CH2CH3 F 4-methoxyphenyl 136 SCH(CH3)2 H O CH2CH3 F 4-methoxyphenyl 137 OCH2CH3 H O CH2CH3 F 4-methoxyphenyl 138 (CH2)2 O CH2CH3 F 4-methoxyphenyl 139 (CH2)4 O CH2CH3 F 4-methoxyphenyl 140 CH3 H O CH2CH3 F 3,4 dichloro phenyl 141 CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 142 CH2CF3 H O CH2CH3 F 3,4 dichloro phenyl 143 CH2CH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 144 CH2CH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 145 cyclopropylmethyl H O CH2CH3 F 3,4 dichloro phenyl 146 SCH(CH3)2 H O CH2CH3 F 3,4 dichloro phenyl 147 OCH2CH3 H O CH2CH3 F 3,4 dichloro phenyl 148 (CH2)2 O CH2CH3 F 3,4 dichloro phenyl 149 (CH2)4 O CH2CH3 F 3,4 dichloro phenyl 150 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 151 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 152 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 153 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 154 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 155 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 156 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 157 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 158 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 159 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]oxadiazolyl 160 CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 161 CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 162 CH2CF3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 163 CH2CH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 164 CH2CH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 165 cyclopropylmethyl H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 166 SCH(CH3)2 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 167 OCH2CH3 H O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 168 (CH2)2 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 169 (CH2)4 O CH2CH3 F 5-benzo[c][1,2,5]thiadiazolyl 170 CH3 H O CH2CF3 F 4-fluorophenyl 171 CH2CH3 H O CH2CF3 F 4-fluorophenyl 172 CH2CF3 H O CH2CF3 F 4-fluorophenyl 173 CH2CH2CH3 H O CH2CF3 F 4-fluorophenyl 174 CH2CH(CH3)2 H O CH2CF3 F 4-fluorophenyl 175 cyclopropylmethyl H O CH2CF3 F 4-fluorophenyl 176 SCH(CH3)2 H O CH2CF3 F 4-fluorophenyl 177 OCH2CH3 H O CH2CF3 F 4-fluorophenyl 178 (CH2)2 O CH2CF3 F 4-fluorophenyl 179 (CH2)4 O CH2CF3 F 4-fluorophenyl 180 CH3 H O CH2CF3 F 4-chlorophenyl 181 CH2CH3 H O CH2CF3 F 4-chlorophenyl 182 CH2CF3 H O CH2CF3 F 4-chlorophenyl 183 CH2CH2CH3 H O CH2CF3 F 4-chlorophenyl 184 CH2CH(CH3)2 H O CH2CF3 F 4-chlorophenyl 185 cyclopropylmethyl H O CH2CF3 F 4-chlorophenyl 186 SCH(CH3)2 H O CH2CF3 F 4-chlorophenyl 187 OCH2CH3 H O CH2CF3 F 4-chlorophenyl 188 (CH2)2 O CH2CF3 F 4-chlorophenyl 189 (CH2)4 O CH2CF3 F 4-chlorophenyl 190 CH3 H O CH2CF3 F 4-trifluoromethylphenyl 191 CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 192 CH2CF3 H O CH2CF3 F 4-trifluoromethylphenyl 193 CH2CH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 194 CH2CH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 195 cyclopropylmethyl H O CH2CF3 F 4-trifluoromethylphenyl 196 SCH(CH3)2 H O CH2CF3 F 4-trifluoromethylphenyl 197 OCH2CH3 H O CH2CF3 F 4-trifluoromethylphenyl 198 (CH2)2 O CH2CF3 F 4-trifluoromethylphenyl 199 (CH2)4 O CH2CF3 F 4-trifluoromethylphenyl 200 CH3 H O CH2CF3 F 4-methoxyphenyl 201 CH2CH3 H O CH2CF3 F 4-methoxyphenyl 202 CH2CF3 H O CH2CF3 F 4-methoxyphenyl 203 CH2CH2CH3 H O CH2CF3 F 4-methoxyphenyl 204 CH2CH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 205 cyclopropylmethyl H O CH2CF3 F 4-methoxyphenyl 206 SCH(CH3)2 H O CH2CF3 F 4-methoxyphenyl 207 OCH2CH3 H O CH2CF3 F 4-methoxyphenyl 208 (CH2)2 O CH2CF3 F 4-methoxyphenyl 209 (CH2)4 O CH2CF3 F 4-methoxyphenyl 210 CH3 H O CH2CF3 F 3,4 dichloro phenyl 211 CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 212 CH2CF3 H O CH2CF3 F 3,4 dichloro phenyl 213 CH2CH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 214 CH2CH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 215 cyclopropylmethyl H O CH2CF3 F 3,4 dichloro phenyl 216 SCH(CH3)2 H O CH2CF3 F 3,4 dichloro phenyl 217 OCH2CH3 H O CH2CF3 F 3,4 dichloro phenyl 218 (CH2)2 O CH2CF3 F 3,4 dichloro phenyl 219 (CH2)4 O CH2CF3 F 3,4 dichloro phenyl 220 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 221 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 222 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 223 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 224 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 225 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 226 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 227 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 228 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 229 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazolyl 230 CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 231 CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 232 CH2CF3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 233 CH2CH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 234 CH2CH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 235 cyclopropylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 236 SCH(CH3)2 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 237 OCH2CH3 H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 238 (CH2)2 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 239 (CH2)4 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazolyl 240 CH3 H O CH2-c-Pr F 4-fluorophenyl 241 CH2CH3 H O CH2-c-Pr F 4-fluorophenyl 242 CH2CF3 H O CH2-c-Pr F 4-fluorophenyl 243 CH2CH2CH3 H O CH2-c-Pr F 4-fluorophenyl 244 CH2CH(CH3)2 H O CH2-c-Pr F 4-fluorophenyl 245 cyclopropylmethyl H O CH2-c-Pr F 4-fluorophenyl 246 SCH(CH3)2 H O CH2-c-Pr F 4-fluorophenyl 247 OCH2CH3 H O CH2-c-Pr F 4-fluorophenyl 248 (CH2)2 O CH2-c-Pr F 4-fluorophenyl 249 (CH2)4 O CH2-c-Pr F 4-fluorophenyl 250 CH3 H O CH2-c-Pr F 4-chlorophenyl 251 CH2CH3 H O CH2-c-Pr F 4-chlorophenyl 252 CH2CF3 H O CH2-c-Pr F 4-chlorophenyl 253 CH2CH2CH3 H O CH2-c-Pr F 4-chlorophenyl 254 CH2CH(CH3)2 H O CH2-c-Pr F 4-chlorophenyl 255 cyclopropylmethyl H O CH2-c-Pr F 4-chlorophenyl 256 SCH(CH3)2 H O CH2-c-Pr F 4-chlorophenyl 257 OCH2CH3 H O CH2-c-Pr F 4-chlorophenyl 258 (CH2)2 O CH2-c-Pr F 4-chlorophenyl 259 (CH2)4 O CH2-c-Pr F 4-chlorophenyl 260 CH3 H O CH2-c-Pr F 4-trifluoromethylphenyl 261 CH2CH3 H O CH2-c-Pr F 4-trifluoromethylphenyl 262 CH2CF3 H O CH2-c-Pr F 4-trifluoromethylphenyl 263 CH2CH2CH3 H O CH2-c-Pr F 4-trifluoromethylphenyl 264 CH2CH(CH3)2 H O CH2-c-Pr F 4-trifluoromethylphenyl 265 cyclopropylmethyl H O CH2-c-Pr F 4-trifluoromethylphenyl 266 SCH(CH3)2 H O CH2-c-Pr F 4-trifluoromethylphenyl 267 OCH2CH3 H O CH2-c-Pr F 4-trifluoromethylphenyl 268 (CH2)2 O CH2-c-Pr F 4-trifluoromethylphenyl 269 (CH2)4 O CH2-c-Pr F 4-trifluoromethylphenyl 270 CH3 H O CH2-c-Pr F 4-methoxyphenyl 271 CH2CH3 H O CH2-c-Pr F 4-methoxyphenyl 272 CH2CF3 H O CH2-c-Pr F 4-methoxyphenyl 273 CH2CH2CH3 H O CH2-c-Pr F 4-methoxyphenyl 274 CH2CH(CH3)2 H O CH2-c-Pr F 4-methoxyphenyl 275 cyclopropylmethyl H O CH2-c-Pr F 4-methoxyphenyl 276 SCH(CH3)2 H O CH2-c-Pr F 4-methoxyphenyl 277 OCH2CH3 H O CH2-c-Pr F 4-methoxyphenyl 278 (CH2)2 O CH2-c-Pr F 4-methoxyphenyl 279 (CH2)4 O CH2-c-Pr F 4-methoxyphenyl 280 CH3 H O CH2-c-Pr F 3,4 dichloro phenyl 281 CH2CH3 H O CH2-c-Pr F 3,4 dichloro phenyl 282 CH2CF3 H O CH2-c-Pr F 3,4 dichloro phenyl 283 CH2CH2CH3 H O CH2-c-Pr F 3,4 dichloro phenyl 284 CH2CH(CH3)2 H O CH2-c-Pr F 3,4 dichloro phenyl 285 cyclopropylmethyl H O CH2-c-Pr F 3,4 dichloro phenyl 286 SCH(CH3)2 H O CH2-c-Pr F 3,4 dichloro phenyl 287 OCH2CH3 H O CH2-c-Pr F 3,4 dichloro phenyl 288 (CH2)2 O CH2-c-Pr F 3,4 dichloro phenyl 289 (CH2)4 O CH2-c-Pr F 3,4 dichloro phenyl 290 CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 291 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 292 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 293 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 294 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 295 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 296 SCH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 297 OCH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 298 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 299 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazolyl 300 CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 301 CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 302 CH2CF3 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 303 CH2CH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 304 CH2CH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 305 cyclopropylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 306 SCH(CH3)2 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 307 OCH2CH3 H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 308 (CH2)2 O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 309 (CH2)4 O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazolyl 310 CH3 H O CH2CH3 Cl 4-fluorophenyl 311 CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 312 CH2CF3 H O CH2CH3 Cl 4-fluorophenyl 313 CH2CH2CH3 H O CH2CH3 Cl 4-fluorophenyl 314 CH2CH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 315 cyclopropylmethyl H O CH2CH3 Cl 4-fluorophenyl 316 SCH(CH3)2 H O CH2CH3 Cl 4-fluorophenyl 317 OCH2CH3 H O CH2CH3 Cl 4-fluorophenyl 318 (CH2)2 O CH2CH3 Cl 4-fluorophenyl 319 (CH2)4 O CH2CH3 Cl 4-fluorophenyl 320 CH3 H O CH2CH3 Cl 4-chlorophenyl 321 CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 322 CH2CF3 H O CH2CH3 Cl 4-chlorophenyl 323 CH2CH2CH3 H O CH2CH3 Cl 4-chlorophenyl 324 CH2CH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 325 cyclopropylmethyl H O CH2CH3 Cl 4-chlorophenyl 326 SCH(CH3)2 H O CH2CH3 Cl 4-chlorophenyl 327 OCH2CH3 H O CH2CH3 Cl 4-chlorophenyl 328 (CH2)2 O CH2CH3 Cl 4-chlorophenyl 329 (CH2)4 O CH2CH3 Cl 4-chlorophenyl 330 CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 331 CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 332 CH2CF3 H O CH2CH3 Cl 4-trifluoromethylphenyl 333 CH2CH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 334 CH2CH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 335 cyclopropylmethyl H O CH2CH3 Cl 4-trifluoromethylphenyl 336 SCH(CH3)2 H O CH2CH3 Cl 4-trifluoromethylphenyl 337 OCH2CH3 H O CH2CH3 Cl 4-trifluoromethylphenyl 338 (CH2)2 O CH2CH3 Cl 4-trifluoromethylphenyl 339 (CH2)4 O CH2CH3 Cl 4-trifluoromethylphenyl 340 CH3 H O CH2CH3 Cl 4-methoxyphenyl 341 CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 342 CH2CF3 H O CH2CH3 Cl 4-methoxyphenyl 343 CH2CH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 344 CH2CH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 345 cyclopropylmethyl H O CH2CH3 Cl 4-methoxyphenyl 346 SCH(CH3)2 H O CH2CH3 Cl 4-methoxyphenyl 347 OCH2CH3 H O CH2CH3 Cl 4-methoxyphenyl 348 (CH2)2 O CH2CH3 Cl 4-methoxyphenyl 349 (CH2)4 O CH2CH3 Cl 4-methoxyphenyl 350 CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 351 CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 352 CH2CF3 H O CH2CH3 Cl 3,4 dichloro phenyl 353 CH2CH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 354 CH2CH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 355 cyclopropylmethyl H O CH2CH3 Cl 3,4 dichloro phenyl 356 SCH(CH3)2 H O CH2CH3 Cl 3,4 dichloro phenyl 357 OCH2CH3 H O CH2CH3 Cl 3,4 dichloro phenyl 358 (CH2)2 O CH2CH3 Cl 3,4 dichloro phenyl 359 (CH2)4 O CH2CH3 Cl 3,4 dichloro phenyl 360 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 361 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 362 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 363 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 364 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 365 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 366 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 367 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 368 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 369 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]oxadiazolyl 370 CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 371 CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 372 CH2CF3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 373 CH2CH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 374 CH2CH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 375 cyclopropylmethyl H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 376 SCH(CH3)2 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 377 OCH2CH3 H O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 378 (CH2)2 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 379 (CH2)4 O CH2CH3 Cl 5-benzo[c][1,2,5]thiadiazolyl 380 CH3 H O CH2CF3 Cl 4-fluorophenyl 381 CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 382 CH2CF3 H O CH2CF3 Cl 4-fluorophenyl 383 CH2CH2CH3 H O CH2CF3 Cl 4-fluorophenyl 384 CH2CH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 385 cyclopropylmethyl H O CH2CF3 Cl 4-fluorophenyl 386 SCH(CH3)2 H O CH2CF3 Cl 4-fluorophenyl 387 OCH2CH3 H O CH2CF3 Cl 4-fluorophenyl 388 (CH2)2 O O CH2CF3 Cl 4-fluorophenyl 389 (CH2)4 O O CH2CF3 Cl 4-fluorophenyl 400 CH3 H O CH2CF3 Cl 4-chlorophenyl 401 CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 402 CH2CF3 H O CH2CF3 Cl 4-chlorophenyl 403 CH2CH2CH3 H O CH2CF3 Cl 4-chlorophenyl 404 CH2CH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 405 cyclopropylmethyl H O CH2CF3 Cl 4-chlorophenyl 406 SCH(CH3)2 H O CH2CF3 Cl 4-chlorophenyl 407 OCH2CH3 H O CH2CF3 Cl 4-chlorophenyl 408 (CH2)2 O CH2CF3 Cl 4-chlorophenyl 409 (CH2)4 O CH2CF3 Cl 4-chlorophenyl 410 CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 411 CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 412 CH2CF3 H O CH2CF3 Cl 4-trifluoromethylphenyl 413 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 416 SCH(CH3)2 H O CH2CF3 Cl 4-trifluoromethylphenyl 417 OCH2CH3 H O CH2CF3 Cl 4-trifluoromethylphenyl 418 (CH2)2 O CH2CF3 Cl 4-trifluoromethylphenyl 419 (CH2)4 O CH2CF3 Cl 4-trifluoromethylphenyl 420 CH3 H O CH2CF3 Cl 4-methoxyphenyl 421 CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 422 CH2CF3 H O CH2CF3 Cl 4-methoxyphenyl 423 CH2CH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 424 CH2CH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 425 cyclopropylmethyl H O CH2CF3 Cl 4-methoxyphenyl 426 SCH(CH3)2 H O CH2CF3 Cl 4-methoxyphenyl 427 OCH2CH3 H O CH2CF3 Cl 4-methoxyphenyl 428 (CH2)2 O CH2CF3 Cl 4-methoxyphenyl 429 (CH2)4 O CH2CF3 Cl 4-methoxyphenyl 430 CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 431 CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 432 CH2CF3 H O CH2CF3 Cl 3,4 dichloro phenyl 433 CH2CH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 434 CH2CH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 435 cyclopropylmethyl H O CH2CF3 Cl 3,4 dichloro phenyl 436 SCH(CH3)2 H O CH2CF3 Cl 3,4 dichloro phenyl 437 OCH2CH3 H O CH2CF3 Cl 3,4 dichloro phenyl 438 (CH2)2 O CH2CF3 Cl 3,4 dichloro phenyl 439 (CH2)4 O CH2CF3 Cl 3,4 dichloro phenyl 440 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 441 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 442 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 443 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 444 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 445 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 446 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 447 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 448 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 449 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazolyl 450 CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 451 CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 452 CH2CF3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 453 CH2CH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 454 CH2CH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 455 cyclopropylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 456 SCH(CH3)2 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 457 OCH2CH3 H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 458 (CH2)2 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 459 (CH2)4 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazolyl 460 CH3 H O CH2-c-Pr Cl 4-fluorophenyl 461 CH2CH3 H O CH2-c-Pr Cl 4-fluorophenyl 462 CH2CF3 H O CH2-c-Pr Cl 4-fluorophenyl 463 CH2CH2CH3 H O CH2-c-Pr Cl 4-fluorophenyl 464 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-fluorophenyl 465 cyclopropylmethyl H O CH2-c-Pr Cl 4-fluorophenyl 466 SCH(CH3)2 H O CH2-c-Pr Cl 4-fluorophenyl 467 OCH2CH3 H O CH2-c-Pr Cl 4-fluorophenyl 468 (CH2)2 O CH2-c-Pr Cl 4-fluorophenyl 469 (CH2)4 O CH2-c-Pr Cl 4-fluorophenyl 470 CH3 H O CH2-c-Pr Cl 4-chlorophenyl 471 CH2CH3 H O CH2-c-Pr Cl 4-chlorophenyl 472 CH2CF3 H O CH2-c-Pr Cl 4-chlorophenyl 473 CH2CH2CH3 H O CH2-c-Pr Cl 4-chlorophenyl 474 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-chlorophenyl 475 cyclopropylmethyl H O CH2-c-Pr Cl 4-chlorophenyl 476 SCH(CH3)2 H O CH2-c-Pr Cl 4-chlorophenyl 477 OCH2CH3 H O CH2-c-Pr Cl 4-chlorophenyl 478 (CH2)2 O CH2-c-Pr Cl 4-chlorophenyl 479 (CH2)4 O CH2-c-Pr Cl 4-chlorophenyl 480 CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 481 CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 482 CH2CF3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 483 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 484 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 485 cyclopropylmethyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 486 SCH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 487 OCH2CH3 H O CH2-c-Pr Cl 4-trifluoromethylphenyl 488 (CH2)2 O CH2-c-Pr Cl 4-trifluoromethylphenyl 489 (CH2)4 O CH2-c-Pr Cl 4-trifluoromethylphenyl 490 CH3 H O CH2-c-Pr Cl 4-methoxyphenyl 491 CH2CH3 H O CH2-c-Pr Cl 4-methoxyphenyl 492 CH2CF3 H O CH2-c-Pr Cl 4-methoxyphenyl 493 CH2CH2CH3 H O CH2-c-Pr Cl 4-methoxyphenyl 494 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-methoxyphenyl 495 cyclopropylmethyl H O CH2-c-Pr Cl 4-methoxyphenyl 496 SCH(CH3)2 H O CH2-c-Pr Cl 4-methoxyphenyl 497 OCH2CH3 H O CH2-c-Pr Cl 4-methoxyphenyl 498 (CH2)2 O CH2-c-Pr Cl 4-methoxyphenyl 499 (CH2)4 O CH2-c-Pr Cl 4-methoxyphenyl 500 CH3 H O CH2-c-Pr Cl 3,4 dichloro phenyl 501 CH2CH3 H O CH2-c-Pr Cl 3,4 dichloro phenyl 502 CH2CF3 H O CH2-c-Pr Cl 3,4 dichloro phenyl 503 CH2CH2CH3 H O CH2-c-Pr Cl 3,4 dichloro phenyl 504 CH2CH(CH3)2 H O CH2-c-Pr Cl 3,4 dichloro phenyl 505 cyclopropylmethyl H O CH2-c-Pr Cl 3,4 dichloro phenyl 506 SCH(CH3)2 H O CH2-c-Pr Cl 3,4 dichloro phenyl 507 OCH2CH3 H O CH2-c-Pr Cl 3,4 dichloro phenyl 508 (CH2)2 O CH2-c-Pr Cl 3,4 dichloro phenyl 509 (CH2)4 O CH2-c-Pr Cl 3,4 dichloro phenyl 510 CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 511 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 512 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 513 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 514 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 515 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 516 SCH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 517 OCH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 518 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 519 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazolyl 520 CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 521 CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 522 CH2CF3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 523 CH2CH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 524 CH2CH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 525 cyclopropylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 526 SCH(CH3)2 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 527 OCH2CH3 H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 528 (CH2)2 O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 529 (CH2)4 O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazolyl 530 CH3 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 531 CH2CH3 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 532 CH2CF3 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 533 CH2CH2CH3 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 534 CH2CH(CH3)2 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 535 cyclopropylmethyl H O CH2-c-Pr NO2 4-trifluoromethylphenyl 536 SCH(CH3)2 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 537 OCH2CH3 H O CH2-c-Pr NO2 4-trifluoromethylphenyl 538 (CH2)2 O CH2-c-Pr NO2 4-trifluoromethylphenyl 539 (CH2)4 O CH2-c-Pr NO2 4-trifluoromethylphenyl 540 CH3 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 541 CH2CH3 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 542 CH2CF3 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 543 CH2CH2CH3 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 544 CH2CH(CH3)2 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 545 cyclopropylmethyl H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 546 SCH(CH3)2 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 547 OCH2CH3 H O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 548 (CH2)2 O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 549 (CH2)4 O CH2-c-Pr NO2 5-benzo[c][1,2,5]oxadiazolyl 550 CH3 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 551 CH2CH3 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 552 CH2CF3 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 553 CH2CH2CH3 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 554 CH2CH(CH3)2 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 555 cyclopropylmethyl H O CH2-c-Pr NH2 4-trifluoromethylphenyl 556 SCH(CH3)2 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 557 OCH2CH3 H O CH2-c-Pr NH2 4-trifluoromethylphenyl 558 (CH2)2 O CH2-c-Pr NH2 4-trifluoromethylphenyl 559 (CH2)4 O CH2-c-Pr NH2 4-trifluoromethylphenyl 980 CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 981 CH2CF3 H O CH2CF3 CF3 4-trifluoromethylphenyl 982 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethylphenyl 985 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethylphenyl 986 (CH2)2 O CH2CF3 CH2CF3 4-trifluoromethylphenyl 987 (CH2)3 O CH2CF3 CH2CF3 4-trifluoromethylphenyl 988 (CH2)4 O CH2CF3 CH2CF3 4-trifluoromethylphenyl 989 (CH2)5 O CH2CF3 CH2CF3 4-trifluoromethylphenyl 990 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-trifluoromethylphenyl 991 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethylphenyl 992 CH2CH3 H O CH2CF3 CF3 4-tolyl 993 CH2CF3 H O CH2CF3 CF3 4-tolyl 994 CH2CH2CH3 H O CH2CF3 CF3 4-tolyl 995 CH2CH(CH3)2 H O CH2CF3 CF3 4-tolyl 996 cyclopropylmethyl H O CH2CF3 CF3 4-tolyl 997 cyclobutylmethyl H O CH2CF3 CF3 4-tolyl 998 (CH2)2 O CH2CF3 CH2CF3 4-tolyl 999 (CH2)3 O CH2CF3 CH2CF3 4-tolyl 1000 (CH2)4 O CH2CF3 CH2CF3 4-tolyl 1001 (CH2)5 O CH2CF3 CH2CF3 4-tolyl 1002 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-tolyl 1003 Cyclopentyl H O CH2CF3 CF3 4-tolyl 1004 CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1005 CH2CF3 H O CH2CF3 CF3 4-ethyl phenyl 1006 CH2CH2CH3 H O CH2CF3 CF3 4-ethyl phenyl 1007 CH2CH(CH3)2 H O CH2CF3 CF3 4-ethyl phenyl 1008 cyclopropylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1009 cyclobutylmethyl H O CH2CF3 CF3 4-ethyl phenyl 1010 (CH2)2 O CH2CF3 CH2CF3 4-ethyl phenyl 1011 (CH2)3 O CH2CF3 CH2CF3 4-ethyl phenyl 1012 (CH2)4 O CH2CF3 CH2CF3 4-ethyl phenyl 1013 (CH2)5 O CH2CF3 CH2CF3 4-ethyl phenyl 1014 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-ethyl phenyl 1015 Cyclopentyl H O CH2CF3 CF3 4-ethyl phenyl 1016 CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1017 CH2CF3 H O CH2CF3 CF3 4-isopropyl phenyl 1018 CH2CH2CH3 H O CH2CF3 CF3 4-isopropyl phenyl 1019 CH2CH(CH3)2 H O CH2CF3 CF3 4-isopropyl phenyl 1020 cyclopropylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1021 cyclobutylmethyl H O CH2CF3 CF3 4-isopropyl phenyl 1022 (CH2)2 O CH2CF3 CH2CF3 4-isopropyl phenyl 1023 (CH2)3 O CH2CF3 CH2CF3 4-isopropyl phenyl 1024 (CH2)4 O CH2CF3 CH2CF3 4-isopropyl phenyl 1025 (CH2)5 O CH2CF3 CH2CF3 4-isopropyl phenyl 1026 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-isopropyl phenyl 1027 Cyclopentyl H O CH2CF3 CF3 4-isopropyl phenyl 1028 CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1029 CH2CF3 H O CH2CF3 CF3 4-thiomethylphenyl 1030 CH2CH2CH3 H O CH2CF3 CF3 4-thiomethylphenyl 1031 CH2CH(CH3)2 H O CH2CF3 CF3 4-thiomethylphenyl 1032 cyclopropylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1033 cyclobutylmethyl H O CH2CF3 CF3 4-thiomethylphenyl 1034 (CH2)2 O CH2CF3 CH2CF3 4-thiomethylphenyl 1035 (CH2)3 O CH2CF3 CH2CF3 4-thiomethylphenyl 1036 (CH2)4 O CH2CF3 CH2CF3 4-thiomethylphenyl 1037 (CH2)5 O CH2CF3 CH2CF3 4-thiomethylphenyl 1038 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-thiomethylphenyl 1039 Cyclopentyl H O CH2CF3 CF3 4-thiomethylphenyl 1040 CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1041 CH2CF3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1042 CH2CH2CH3 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1043 CH2CH(CH3)2 H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1044 cyclopropylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1045 cyclobutylmethyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1046 (CH2)2 O CH2CF3 CH2CF3 4-trifluoromethoxyphenyl 1047 (CH2)3 O CH2CF3 CH2CF3 4-trifluoromethoxyphenyl 1048 (CH2)4 O CH2CF3 CH2CF3 4-trifluoromethoxyphenyl 1049 (CH2)5 O CH2CF3 CH2CF3 4-trifluoromethoxyphenyl 1050 5,5-spiro[2.3]hexane O CH2CF3 CH2CF3 4-trifluoromethoxyphenyl 1051 Cyclopentyl H O CH2CF3 CF3 4-trifluoromethoxyphenyl 1052 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1053 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1054 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1055 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1056 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1057 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1058 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1059 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1060 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1061 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethylphenyl 1062 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethylphenyl 1063 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethylphenyl 1064 CH2CH3 H O CH2-c-Pr CF3 4-tolyl 1065 CH2CF3 H O CH2-c-Pr CF3 4-tolyl 1066 CH2CH2CH3 H O CH2-c-Pr CF3 4-tolyl 1067 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-tolyl 1068 cyclopropylmethyl H O CH2-c-Pr CF3 4-tolyl 1069 cyclobutylmethyl H O CH2-c-Pr CF3 4-tolyl 1070 (CH2)2 O CH2-c-Pr CF3 4-tolyl 1071 (CH2)3 O CH2-c-Pr CF3 4-tolyl 1072 (CH2)4 O CH2-c-Pr CF3 4-tolyl 1073 (CH2)5 O CH2-c-Pr CF3 4-tolyl 1074 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-tolyl 1075 Cyclopentyl H O CH2-c-Pr CF3 4-tolyl 1076 CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 1077 CH2CF3 H O CH2-c-Pr CF3 4-ethyl phenyl 1078 CH2CH2CH3 H O CH2-c-Pr CF3 4-ethyl phenyl 1079 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-ethyl phenyl 1080 cyclopropylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 1081 cyclobutylmethyl H O CH2-c-Pr CF3 4-ethyl phenyl 1082 (CH2)2 O CH2-c-Pr CF3 4-ethyl phenyl 1083 (CH2)3 O CH2-c-Pr CF3 4-ethyl phenyl 1084 (CH2)4 O CH2-c-Pr CF3 4-ethyl phenyl 1085 (CH2)5 O CH2-c-Pr CF3 4-ethyl phenyl 1086 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-ethyl phenyl 1087 Cyclopentyl H O CH2-c-Pr CF3 4-ethyl phenyl 1088 CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1089 CH2CF3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1090 CH2CH2CH3 H O CH2-c-Pr CF3 4-isopropyl phenyl 1091 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-isopropyl phenyl 1092 cyclopropylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1093 cyclobutylmethyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1094 (CH2)2 O CH2-c-Pr CF3 4-isopropyl phenyl 1095 (CH2)3 O CH2-c-Pr CF3 4-isopropyl phenyl 1096 (CH2)4 O CH2-c-Pr CF3 4-isopropyl phenyl 1097 (CH2)5 O CH2-c-Pr CF3 4-isopropyl phenyl 1098 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-isopropyl phenyl 1099 Cyclopentyl H O CH2-c-Pr CF3 4-isopropyl phenyl 1100 CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1101 CH2CF3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1102 CH2CH2CH3 H O CH2-c-Pr CF3 4-thiomethylphenyl 1103 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-thiomethylphenyl 1104 cyclopropylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1105 cyclobutylmethyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1106 (CH2)2 O CH2-c-Pr CF3 4-thiomethylphenyl 1107 (CH2)3 O CH2-c-Pr CF3 4-thiomethylphenyl 1108 (CH2)4 O CH2-c-Pr CF3 4-thiomethylphenyl 1109 (CH2)5 O CH2-c-Pr CF3 4-thiomethylphenyl 1110 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-thiomethylphenyl 1111 Cyclopentyl H O CH2-c-Pr CF3 4-thiomethylphenyl 1112 CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1113 CH2CF3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1114 CH2CH2CH3 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1115 CH2CH(CH3)2 H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1116 cyclopropylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1117 cyclobutylmethyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1118 (CH2)2 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1119 (CH2)3 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1120 (CH2)4 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1121 (CH2)5 O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1122 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1123 Cyclopentyl H O CH2-c-Pr CF3 4-trifluoromethoxyphenyl 1124 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1125 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1126 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1127 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1128 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1129 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1130 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1131 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1132 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1133 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1134 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1135 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1136 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1137 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1138 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1139 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1140 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1141 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1142 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1143 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1144 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1145 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1146 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1147 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1148 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1149 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1150 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1151 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1152 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1153 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1154 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 1155 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 1156 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 1157 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 1158 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 1159 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1160 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1161 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1162 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1163 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1164 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1165 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1166 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1167 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1168 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1169 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1170 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 1171 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1172 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1173 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1174 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1175 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1176 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1177 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1178 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1179 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1180 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1181 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1182 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 1183 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1184 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1185 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1186 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1187 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1188 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1189 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1190 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1191 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1192 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1193 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1194 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1195 Cyclopentyl H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1196 CH2CH3 H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1197 CH2CF3 H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1198 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1199 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1200 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1201 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1202 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1203 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1204 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1205 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1206 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1207 Cyclopentyl H O OCH2CF3 OCH2CF3 4-trifluoromethylphenyl 1208 CH2CH3 H O OCH2CF3 OCH2CF3 4-tolyl 1209 CH2CF3 H O OCH2CF3 OCH2CF3 4-tolyl 1210 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-tolyl 1211 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-tolyl 1212 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-tolyl 1213 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-tolyl 1214 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 1215 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 1216 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 1217 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 1218 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 1219 Cyclopentyl H O OCH2CF3 OCH2CF3 4-tolyl 1220 CH2CH3 H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1221 CH2CF3 H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1222 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1223 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1224 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1225 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1226 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1227 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1228 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1229 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1230 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1231 Cyclopentyl H O OCH2CF3 OCH2CF3 4-ethyl phenyl 1232 CH2CH3 H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1233 CH2CF3 H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1234 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1235 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1236 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1237 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1238 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1239 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1240 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1241 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1242 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1243 Cyclopentyl H O OCH2CF3 OCH2CF3 4-isopropyl phenyl 1244 CH2CH3 H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1245 CH2CF3 H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1246 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1247 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1248 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1249 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1250 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1251 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1252 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1253 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1254 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1255 Cyclopentyl H O OCH2CF3 OCH2CF3 4-thiomethylphenyl 1256 CH2CH3 H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1257 CH2CF3 H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1258 CH2CH2CH3 H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1259 CH2CH(CH3)2 H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1260 cyclopropylmethyl H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1261 cyclobutylmethyl H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1262 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1263 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1264 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1265 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1266 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1267 Cyclopentyl H O OCH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1269 (CH2)3 O CH2CF3 Cl 4-trifluoromethylphenyl 1270 (CH2)5 O CH2CF3 Cl 4-trifluoromethylphenyl 1271 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethylphenyl 1273 CH2CH3 H O CH2CF3 Cl 4-tolyl 1274 CH2CF3 H O CH2CF3 Cl 4-tolyl 1275 CH2CH2CH3 H O CH2CF3 Cl 4-tolyl 1276 CH2CH(CH3)2 H O CH2CF3 Cl 4-tolyl 1277 cyclopropylmethyl H O CH2CF3 Cl 4-tolyl 1278 cyclobutylmethyl H O CH2CF3 Cl 4-tolyl 1279 (CH2)2 O CH2CF3 Cl 4-tolyl 1280 (CH2)3 O CH2CF3 Cl 4-tolyl 1281 (CH2)4 O CH2CF3 Cl 4-tolyl 1282 (CH2)5 O CH2CF3 Cl 4-tolyl 1283 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-tolyl 1284 Cyclopentyl H O CH2CF3 Cl 4-tolyl 1285 CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1286 CH2CF3 H O CH2CF3 Cl 4-ethyl phenyl 1287 CH2CH2CH3 H O CH2CF3 Cl 4-ethyl phenyl 1288 CH2CH(CH3)2 H O CH2CF3 Cl 4-ethyl phenyl 1289 cyclopropylmethyl H O CH2CF3 Cl 4-ethyl phenyl 1290 cyclobutylmethyl O CH2CF3 Cl 4-ethyl phenyl 1291 (CH2)2 O CH2CF3 Cl 4-ethyl phenyl 1292 (CH2)3 O CH2CF3 Cl 4-ethyl phenyl 1293 (CH2)4 O CH2CF3 Cl 4-ethyl phenyl 1294 (CH2)5 O CH2CF3 Cl 4-ethyl phenyl 1295 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-ethyl phenyl 1296 Cyclopentyl H O CH2CF3 Cl 4-ethyl phenyl 1297 CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1298 CH2CF3 H O CH2CF3 Cl 4-isopropyl phenyl 1299 CH2CH2CH3 H O CH2CF3 Cl 4-isopropyl phenyl 1303 (CH2)2 O CH2CF3 Cl 4-isopropyl phenyl 1304 (CH2)3 O CH2CF3 Cl 4-isopropyl phenyl 1305 (CH2)4 O CH2CF3 Cl 4-isopropyl phenyl 1306 (CH2)5 O CH2CF3 Cl 4-isopropyl phenyl 1307 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-isopropyl phenyl 1309 CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1310 CH2CF3 H O CH2CF3 Cl 4-thiomethylphenyl 1311 CH2CH2CH3 H O CH2CF3 Cl 4-thiomethylphenyl 1315 (CH2)2 O CH2CF3 Cl 4-thiomethylphenyl 1316 (CH2)3 O CH2CF3 Cl 4-thiomethylphenyl 1317 (CH2)4 O CH2CF3 Cl 4-thiomethylphenyl 1318 (CH2)5 O CH2CF3 Cl 4-thiomethylphenyl 1319 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-thiomethylphenyl 1321 CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1322 CH2CF3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1323 CH2CH2CH3 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1324 CH2CH(CH3)2 H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1325 cyclopropylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1326 cyclobutylmethyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1327 (CH2)2 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1328 (CH2)3 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1329 (CH2)4 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1330 (CH2)5 O CH2CF3 Cl 4-trifluoromethoxyphenyl 1331 5,5-spiro[2.3]hexane O CH2CF3 Cl 4-trifluoromethoxyphenyl 1332 Cyclopentyl H O CH2CF3 Cl 4-trifluoromethoxyphenyl 1333 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1334 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1335 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethylphenyl 1336 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethylphenyl 1337 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethylphenyl 1338 CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1339 CH2CF3 H O CH2-c-Pr Cl 4-tolyl 1340 CH2CH2CH3 H O CH2-c-Pr Cl 4-tolyl 1341 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-tolyl 1342 cyclopropylmethyl H O CH2-c-Pr Cl 4-tolyl 1343 cyclobutylmethyl H O CH2-c-Pr Cl 4-tolyl 1344 (CH2)2 O CH2-c-Pr Cl 4-tolyl 1345 (CH2)3 O CH2-c-Pr Cl 4-tolyl 1346 (CH2)4 O CH2-c-Pr Cl 4-tolyl 1347 (CH2)5 O CH2-c-Pr Cl 4-tolyl 1348 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-tolyl 1349 Cyclopentyl H O CH2-c-Pr Cl 4-tolyl 1350 CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1351 CH2CF3 H O CH2-c-Pr Cl 4-ethyl phenyl 1352 CH2CH2CH3 H O CH2-c-Pr Cl 4-ethyl phenyl 1353 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-ethyl phenyl 1354 cyclopropylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1355 cyclobutylmethyl H O CH2-c-Pr Cl 4-ethyl phenyl 1356 (CH2)2 O CH2-c-Pr Cl 4-ethyl phenyl 1357 (CH2)3 O CH2-c-Pr Cl 4-ethyl phenyl 1358 (CH2)4 O CH2-c-Pr Cl 4-ethyl phenyl 1359 (CH2)5 O CH2-c-Pr Cl 4-ethyl phenyl 1360 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-ethyl phenyl 1361 Cyclopentyl H O CH2-c-Pr Cl 4-ethyl phenyl 1362 CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1363 CH2CF3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1364 CH2CH2CH3 H O CH2-c-Pr Cl 4-isopropyl phenyl 1365 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-isopropyl phenyl 1366 cyclopropylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1367 cyclobutylmethyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1368 (CH2)2 O CH2-c-Pr Cl 4-isopropyl phenyl 1369 (CH2)3 O CH2-c-Pr Cl 4-isopropyl phenyl 1370 (CH2)4 O CH2-c-Pr Cl 4-isopropyl phenyl 1371 (CH2)5 O CH2-c-Pr Cl 4-isopropyl phenyl 1372 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-isopropyl phenyl 1373 Cyclopentyl H O CH2-c-Pr Cl 4-isopropyl phenyl 1374 CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1375 CH2CF3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1376 CH2CH2CH3 H O CH2-c-Pr Cl 4-thiomethylphenyl 1377 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-thiomethylphenyl 1378 cyclopropylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1379 cyclobutylmethyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1380 (CH2)2 O CH2-c-Pr Cl 4-thiomethylphenyl 1381 (CH2)3 O CH2-c-Pr Cl 4-thiomethylphenyl 1382 (CH2)4 O CH2-c-Pr Cl 4-thiomethylphenyl 1383 (CH2)5 O CH2-c-Pr Cl 4-thiomethylphenyl 1384 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-thiomethylphenyl 1385 Cyclopentyl H O CH2-c-Pr Cl 4-thiomethylphenyl 1386 CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1387 CH2CF3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1388 CH2CH2CH3 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1389 CH2CH(CH3)2 H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1390 cyclopropylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1391 cyclobutylmethyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1392 (CH2)2 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1393 (CH2)3 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1394 (CH2)4 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1395 (CH2)5 O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1396 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1397 Cyclopentyl H O CH2-c-Pr Cl 4-trifluoromethoxyphenyl 1398 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1399 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1400 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1401 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1402 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1403 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1404 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1405 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1406 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1407 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1408 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1409 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethylphenyl 1410 CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1411 CH2CF3 H O CH2CF3 OCH2CF3 4-tolyl 1412 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-tolyl 1413 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-tolyl 1414 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1415 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-tolyl 1416 (CH2)2 O CH2CF3 OCH2CF3 4-tolyl 1417 (CH2)3 O CH2CF3 OCH2CF3 4-tolyl 1418 (CH2)4 O CH2CF3 OCH2CF3 4-tolyl 1419 (CH2)5 O CH2CF3 OCH2CF3 4-tolyl 1420 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-tolyl 1421 Cyclopentyl H O CH2CF3 OCH2CF3 4-tolyl 1422 CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1423 CH2CF3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1424 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1425 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-ethyl phenyl 1426 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1427 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1428 (CH2)2 O CH2CF3 OCH2CF3 4-ethyl phenyl 1429 (CH2)3 O CH2CF3 OCH2CF3 4-ethyl phenyl 1430 (CH2)4 O CH2CF3 OCH2CF3 4-ethyl phenyl 1431 (CH2)5 O CH2CF3 OCH2CF3 4-ethyl phenyl 1432 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-ethyl phenyl 1433 Cyclopentyl H O CH2CF3 OCH2CF3 4-ethyl phenyl 1434 CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1435 CH2CF3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1436 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1437 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1438 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1439 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1440 (CH2)2 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1441 (CH2)3 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1442 (CH2)4 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1443 (CH2)5 O CH2CF3 OCH2CF3 4-isopropyl phenyl 1444 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-isopropyl phenyl 1445 Cyclopentyl H O CH2CF3 OCH2CF3 4-isopropyl phenyl 1446 CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1447 CH2CF3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1448 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1449 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1450 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1451 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1452 (CH2)2 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1453 (CH2)3 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1454 (CH2)4 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1455 (CH2)5 O CH2CF3 OCH2CF3 4-thiomethylphenyl 1456 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-thiomethylphenyl 1457 Cyclopentyl H O CH2CF3 OCH2CF3 4-thiomethylphenyl 1458 CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1459 CH2CF3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1460 CH2CH2CH3 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1461 CH2CH(CH3)2 H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1462 cyclopropylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1463 cyclobutylmethyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1464 (CH2)2 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1465 (CH2)3 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1466 (CH2)4 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1467 (CH2)5 O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1468 5,5-spiro[2.3]hexane O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1469 Cyclopentyl H O CH2CF3 OCH2CF3 4-trifluoromethoxyphenyl 1470 CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1471 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1472 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1473 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1474 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1475 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1476 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1477 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1478 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1479 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1480 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1481 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-trifluoromethylphenyl 1482 CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1483 CH2CF3 H O CH2-c-Pr OCH2CF3 4-tolyl 1484 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-tolyl 1485 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-tolyl 1486 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1487 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-tolyl 1488 (CH2)2 O CH2-c-Pr OCH2CF3 4-tolyl 1489 (CH2)3 O CH2-c-Pr OCH2CF3 4-tolyl 1490 (CH2)4 O CH2-c-Pr OCH2CF3 4-tolyl 1491 (CH2)5 O CH2-c-Pr OCH2CF3 4-tolyl 1492 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-tolyl 1493 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-tolyl 1494 CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1495 CH2CF3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1496 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1497 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1498 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1499 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1500 (CH2)2 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1501 (CH2)3 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1502 (CH2)4 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1503 (CH2)5 O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1504 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1505 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-ethyl phenyl 1506 CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1507 CH2CF3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1508 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1509 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1510 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1511 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1512 (CH2)2 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1513 (CH2)3 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1514 (CH2)4 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1515 (CH2)5 O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1516 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1517 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-isopropyl phenyl 1518 CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1519 CH2CF3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1520 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1521 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1522 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1523 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1524 (CH2)2 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1525 (CH2)3 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1526 (CH2)4 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1527 (CH2)5 O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1528 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1529 Cyclopentyl H O CH2-c-Pr OCH2CF3 4-thiomethylphenyl 1529a CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1530 CH2CF3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1531 CH2CH2CH3 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1532 CH2CH(CH3)2 H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1533 cyclopropylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1534 cyclobutylmethyl H O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1535 (CH2)2 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1536 (CH2)3 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1537 (CH2)4 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1538 (CH2)5 O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1539 5,5-spiro[2.3]hexane O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 1540 Cyclopentyl O CH2-c-Pr OCH2CF3 4-trifluoromethoxyphenyl 2704 CH2CH3 H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2705 CH2CF3 H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2706 CH2CH2CH3 H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2707 CH2CH(CH3)2 H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2708 cyclopropylmethyl H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2709 cyclobutylmethyl H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2710 (CH2)2 O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2711 (CH2)3 O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2712 (CH2)4 O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2713 (CH2)5 O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2714 5,5-spiro[2.3]hexane O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2715 Cyclopentyl H O CH2CH2CF3 Cl 4-trifluoromethylphenyl 2716 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2717 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2718 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2721 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2722 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2723 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2724 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2725 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2726 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2727 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5]oxadiazole 2733 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazole 2735 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazole 2737 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5]oxadiazole 2738 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5]oxadiazole 2739 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5]oxadiazole 2745 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazole 2747 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazole 2749 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazole 2750 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazole 2751 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5]oxadiazole 2752 CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2753 CH2CF3 H O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2754 CH2CH2CH3 H O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2757 cyclobutylmethyl H O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2758 (CH2)2 O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2759 (CH2)3 O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2760 (CH2)4 O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2761 (CH2)5 O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2762 5,5-spiro[2.3]hexane O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2763 Cyclopentyl H O CH2CF3 CF3 5-benzo[c][1,2,5]thiadiazole 2769 cyclobutylmethyl H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazole 2771 (CH2)3 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazole 2773 (CH2)5 O CH2CF3 F 5-benzo[c][1,2,5]thiadiazole 2774 5,5-spiro[2.3]hexane O CH2CF3 F 5-benzo[c][1,2,5]thiadiazole 2775 Cyclopentyl H O CH2CF3 F 5-benzo[c][1,2,5]thiadiazole 2781 cyclobutylmethyl H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazole 2783 (CH2)3 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazole 2785 (CH2)5 O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazole 2786 5,5-spiro[2.3]hexane O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazole 2787 Cyclopentyl H O CH2CF3 Cl 5-benzo[c][1,2,5]thiadiazole 2788 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2789 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2790 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2791 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2792 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2793 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2794 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2795 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2796 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2797 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2798 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2799 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]oxadiazole 2805 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazole 2807 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazole 2809 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazole 2810 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazole 2811 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5]oxadiazole 2817 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazole 2819 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazole 2821 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazole 2822 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazole 2823 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]oxadiazole 2824 CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2825 CH2CF3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2826 CH2CH2CH3 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2827 CH2CH(CH3)2 H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2828 cyclopropylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2829 cyclobutylmethyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2830 (CH2)2 O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2831 (CH2)3 O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2832 (CH2)4 O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2833 (CH2)5 O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2834 5,5-spiro[2.3]hexane O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2835 Cyclopentyl H O CH2-c-Pr CF3 5-benzo[c][1,2,5]thiadiazole 2841 cyclobutylmethyl H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazole 2843 (CH2)3 O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazole 2845 (CH2)5 O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazole 2846 5,5-spiro[2.3]hexane O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazole 2847 Cyclopentyl H O CH2-c-Pr F 5-benzo[c][1,2,5]thiadiazole 2853 cyclobutylmethyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazole 2855 (CH2)3 O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazole 2857 (CH2)5 O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazole 2858 5,5-spiro[2.3]hexane O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazole 2859 Cyclopentyl H O CH2-c-Pr Cl 5-benzo[c][1,2,5]thiadiazole;
