Benzazepine derivatives for the treatment of neurological disorders

The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Piperazine Derivatives Useful for the Treatment of Gastrointestinal Disorders

The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Ra, Rb, Rc, Rd, Re, Rf and Y are as defined in the specification. The compounds are partial or full agonists at the growth hormone secretagogue (GHS) receptors. Pharmaceutical compositions comprising the compounds methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.

Pyrazolo[3,4-c]pyridines as gsk-3 inhibitors

A compound of formula (I) or a derivative thereof, wherein R1 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclyalkyl wherein the heterocyclyl and the alkyl moieties may each independently be unsubstituted or substituted; and R2 is unsubstituted or substituted aryl or unsubstituted or substituted heteroaryl, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds and composition in medicine.

Derivatives of Imidazo [1,2-A] Pyridine Useful as Medicaments For Treating Gastrointestinal Diseases

Disclosed are imidazopyridine compounds having the formula: ...

Benzodiazepine bromodomain inhibitor

Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

Benzazepine derivatives for the treatment of neurological disorders

The present invention relates to benzazepine derivatives of formula (I) wherein: R1 represents C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

NOVEL COMPOUNDS

Benzodiazepine compounds of formula (I) 2. A compound or a salt thereof according to claim 1 , wherein Ris methyl.3. A compound or a salt thereof according to claim 1 , wherein Ris —ORand Ris Calkyl.4. A compound or a salt thereof according to claim 1 , wherein Ris —NRR.5. A compound or a salt thereof according to claim 4 , wherein Ris hydrogen and Ris Calkyl.6. A compound or a salt thereof according to claim 4 , wherein Ris selected from RRN—CH— claim 4 , RRN—CHCH— claim 4 , RRN—CHCHCH— and RRN—CHCHCHCH— claim 4 , and wherein Rand Rare selected from hydrogen and methyl.9. A compound or a salt thereof according to claim 1 , wherein Ris 8-MeO.10. A compound or a salt thereof according to wherein the chiral carbon atom depicted by * is the S-enantiomer.11. A compound or a salt thereof according to which is any one of Examples 1-82 or a salt thereof.13. A pharmaceutical composition which comprises a compound or a salt thereof according to and one or more pharmaceutically acceptable carriers claim 12 , diluents or excipients.14. A combination pharmaceutical product comprising a compound or a salt thereof according to together with one or more other therapeutically active agents.15. A method for treatment of a disease or condition claim 12 , for which a bromodomain inhibitor is indicated claim 12 , in a subject in need thereof which comprises administering a therapeutically effective amount of compound or a salt thereof according to .16. A method for treatment according to claim 15 , wherein the disease or condition is a chronic autoimmune and/or inflammatory condition.17. A method for treatment according to claim 15 , wherein the disease or condition is cancer.18. A method for treatment according to claim 15 , wherein the subject is a human.19. A method for inhibiting a bromodomain which comprises contacting the bromodomain with a compound or a salt thereof according to . The present invention relates to benzodiazepine compounds, pharmaceutical compositions containing ...

Benzodiazepine Bromodomain Inhibitor

Benzodiazepine compounds of formula (I) 1. A compound of formula (I) or a salt thereofwhere{'sup': '1', 'sub': '1-3', 'Ris Calkyl;'}{'sup': 2', '2a', '2a′', '2b, 'Ris —NRR or —OR;'}{'sup': 2a', '2′a', '2b', '2a', '2′a', '2c', '2′c, 'sub': 1-6', '1-6', '1-6', '1-4', '1-4, 'wherein one of Ror Ris hydrogen, and Ror the other of Ror Ris selected from Calkyl, haloCalkyl, RRN—Calkyl, carbocyclyl, carbocyclylCalkyl, heterocyclyl and heterocyclylCalkyl,'}{'sub': 1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6', '1-6, 'wherein any of the carbocyclyl or heterocyclyl groups are optionally substituted by one or more groups selected from halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, carbonyl, —CO-carbocyclyl, azido, amino, hydroxyl, nitro and cyano, wherein the —CO-carbocyclyl group may be optionally substituted by one or more groups selected from halogen, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, azido, nitro and cyano;'}{'sup': 2a', '2′a, 'sub': '1-6', 'or two adjacent groups on any of the carbocyclyl or heterocyclyl groups together with the interconnecting atoms form a 5- or 6-membered ring which ring may contain 1 or 2 heteroatoms independently selected from O, S and N; or Rand Rtogether with the N-atom to which they are attached form a 4-, 5-, 6- or 7-membered ring which optionally contains 1 or 2 heteroatoms independently selected from O, S and N; wherein the 4-, 5-, 6- or 7-membered ring is optionally substituted by Calkyl, hydroxyl or amino;'}{'sup': 2c', '2′c, 'sub': '1-6', 'Rand Rare independently hydrogen or Calkyl;'}{'sup': 3', '6', '7, 'sub': 1-6', '1-6', '1-6', '1-6', '3', '3', '1-4', '1-4, 'each Ris independently selected from hydrogen, hydroxyl, halo, Calkyl, halo Calkyl, Calkoxy, halo Calkoxy, nitro, cyano, CF, —OCF, —COORS, -—CalkylNRRand —CalkylOH;'}{'sup': 4', '5, 'sub': 1-6', '1-6', '1-6', '1-6', '3', '3', '2', '1-4, 'Ris hydroxyl, halo, Calkyl, haloCalkyl, Calkoxy, haloCalkoxy, nitro, cyano, CF, —OCF, —COOR; or —OS(O)Calkyl;'}{'sup': '5', 'sub': '1-3', ' ...

Medicaments

A method of treating an Msk-1 and/or ROCK(1 and 2) mediated disease or condition in a mammal comprising administration of an effective amount of a compounds of the formula (I) and physiologically acceptable salts thereof wherein, R1 is a 5, or 6 membered heterocyclic group selected from group a, b, c or d wherein X1 is a group selected from N or CR7 and X2 is a group selected from O, S or NR8; X3 and X4 which may be the same or different is a group selected from N or CR7; X5 is a group selected from O, S or NR8 and X6 is N or CR7; X7, X8 and X9 may be the same or different and selected from a group N or CR7, pharmaceutical compositions, novel compounds and processes for their preparation.

Protease inhibitors

The invention relates to 3-hydroxy-and 3-keto-cyclohetero-substituted leucine compounds that are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor. The 3-hydroxy-or 3-keto-moiety is bonded to a tetrahydrothiophene, tetrahydrothiopyran, tetrahydrofuran or tetrahydropyran ring.

Pyrazolopyridines and pyrazolopyridazines as antidiabetics

The present invention includes compound of formula (I), or a derivative thereof, wherein Y is CH or N; R¹ is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl, and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclyl and the alkyl moieties may each independently be unsubstituted or substituted; and R² is unsubstituted aryl or unsubstituted or substituted or substituted heteroaryl. Additionally the present invention includes a process for preparing such a compound, a pharmaceutical composition containing such a compound, and the use of such a compound in medicine.

Piperazine derivatives useful for the treatment of gastrointestinal disorders

The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R a , R b , R c , R d , R e , R f and Y are as defined in the specification. The compounds are partial or full agonists at the growth hormone secretagogue (GHS) receptors. Pharmaceutical compositions comprising the compounds methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.

OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (SIP)

The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

NOVEL COMPOUNDS

The present invention relates to compounds of formula (I) processes for their preparation, pharmaceutical compositions containing the same and to their use in the treatment of gastrointestinal and other disorders.

Oxadiazole derivatives active on sphingosine-1-phosphate (S1P)

The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

Protease inhibitors

The invention relates to 3-hydroxy-and 3-keto-cyclohetero-substituted leucine compounds that are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor. The 3-hydroxy-or 3-keto-moiety is bonded to a tetrahydrothiophene, tetrahydrothiopyran, tetrahydrofuran or tetrahydropyran ring.

Benzazepine derivatives for the treatment of neurological and psychiatric disorders

The present invention relates to novel benzazepine derivatives of formula (I); wherein: R1 represents —C3-7 cycloalkyl optionally substituted by C1-3 alkyl; R2 represents -aryl, -heterocyclyl, heteroaryl, -aryl-X—C3-8 cycloalkyl, cycloalkyl, -aryl-X-aryl, -aryl-X-heteroaryl, -aryl-X-heterocyclyl, -heteroaryl-X—C3-8 cycloalkyl, -heteroaryl-X-aryl, -heteroaryl-X-heteroaryl, -heteroaryl-X-heterocyclyl, -heterocyclyl-X—C3-8 cyclooalkyl, -heterocyclyl-X-aryl, -heterocyclyl-X-heteroaryl or -heterocyclyl-X-heterocyclyl; X represents a bond, O, CO, —CH2O—, —COCH2—, —COCH2O—, —CONR2b—, —COCH2NR2bCO—, —CSNH—, SO2, —SO2C1-3 alkyl-, —SO2C2-3 alkenyl-, —COC2-3 alkenyl-, —CO—C(R2a)(R2b)— or —CO—C(R2a)(R2b)CH2—; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Pyrazolopyridines and pyrazolopyridazines as antidiabetics

The present invention includes compound of formula (I), or a derivative thereof, wherein Y is CH or N; R¹ is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl, and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclcyl and the alkyl moieties may each inedepently be unsubstituted or substituted; and R² is unsubstituted aryl or unsubstituted or substituted or substituted heteroaryl. Additionally the present invention inlcudes a process for preparing such a compound, a pharmaceutical composition containing such a compound, and the use of such a compound in medicine.

Benzazepine Derivatives For The Treatment of Neurological Disorders

The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

BENZAZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

The present invention relates to benzazepine derivatives of formula (I) wherein: R1 represents —C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

COVALENT CONJUGATES

The present invention relates to covalent conjugates of BET inhibitors and alpha amino acid esters, processes for their preparation, compositions containing them, and to their use in the treatment of various disorders in particular inflammatory and autoimmune diseases, such as rheumatoid arthritis; and cancers. 1. A covalent conjugate of a BET inhibitor and an alpha amino acid ester , wherein the ester group of the alpha amino acid ester is hydrolysable by one or more intracellular carboxylesterases to the corresponding carboxylic acid , and wherein the alpha amino acid ester possesses a rate of hydrolysis of between 0.2 to 0.5 μM/min/μM.2. The covalent conjugate according to claim 1 , wherein the alpha amino acid ester is conjugated to the BET inhibitor such that the potency of the covalent conjugate in an in vitro binding assay is no less than 50% of the potency of the unconjugated BET inhibitor in the same assay.3. The covalent conjugate according to claim 2 , wherein the alpha amino acid ester is conjugated to the BET inhibitor such that the potency of the covalent conjugate in an in vitro binding assay is at least as high as that of the unconjugated BET inhibitor in the same assay.5. The covalent conjugate according to claim 4 , wherein Rrepresents hydrogen claim 4 , Calkyl claim 4 , —(CH)cycloalkyl claim 4 , —(CH)heterocycloalkyl claim 4 , or —CRRR claim 4 , and further wherein Ris hydrogen claim 4 , hydroxyl claim 4 , —CHOH claim 4 , —CHCalkyl claim 4 , halo claim 4 , —COOH claim 4 , —CONH claim 4 , 1H-imidazol-4-yl claim 4 , —SH claim 4 , —SeH claim 4 , Calkyl claim 4 , Calkoxy claim 4 , phenyl claim 4 , or 4-hydroxyphenyl wherein said Calkyl or Calkoxy may be optionally substituted with halo claim 4 , hydroxyl claim 4 , —NHC(═NH)NH claim 4 , —NH claim 4 , —COOH claim 4 , —CONH claim 4 , or —SCH claim 4 , and Rand Rare each independently hydrogen or Calkyl claim 4 , and c is 0 claim 4 , 1 or 2.7. The covalent conjugate according to claim 4 , wherein ...

THIADIAZOLE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF DISORDERS MEDIATED BY S1P1 RECEPTORS

The present invention relates to novel compounds having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

Alpha-4 Integrin Mediated Cell Adhesion Inhibitors for the Treatment or Prevention of Inflammatory Diseases

The present invention relates to novel compounds of formula (I), processes for their preparation, compositions comprising them and their use in the treatment or prevention of diseases capable of being modulated by the inhibition of cell adhesion.

IMIDAZOPYRIDINE DERIVATIVES AS ACID PUMP ANTAGONISTS

This invention relates to newly identified imidazopyridine compounds of formula (I), to the use of such compounds in treating GERD and the like.

Pyrazolopyridines and pyrazolopyridazines as antidabetics

The present invention includes compound of formula (I), or a derivative thereof, wherein Y is CH or N; R1 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl, and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclyl and the alkyl moieties may each independently be unsubstituted or substituted; and R2 is unsubstituted aryl or unsubstituted or substituted or substituted heteroaryl. Additionally the present invention includes a process for preparing such a compound, a pharmaceutical composition containing such a compound, and the use of such a compound in medicine.

ARYL AND HETEROARYL SULPHONAMIDES AS GROWTH HORMONE SECRETAGOGUE RECEPTOR AGONISTS

The present invention therefore provides compounds of formula (I) or pharmaceutically acceptable salts thereof: (I) processes for their preparation, pharmaceutical compositions containing the same and to their use in the treatment of gastrointestinal and other disorders.

BENZAZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Pyrazolo[3,4-c]pyridines as gsk-3 inhibitors

The present invention relates to novel compounds, in particular to novel pyrazolopyridine derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds in medicine.

Compounds

The present invention relates to novel pyridone derivatives capable of inhibiting alpha₄ integrin mediated cell adhesion, processes for their preparation, compositions comprising them and their use in the treatment of diseases capable of being modulated by the inhibition of cell adhesion.

Imidazopyridine derivatives as kinase inhibitors

A compound of the formula and physiologically acceptable salts and or N-oxides thereof wherein, X1 is N or CR3; X2 is N or CR4; X3 is N or CR5; X4 is N or CR6. with the proviso that at least one but not more than two of X1, X2, X3 and X4 represents N. R1 is a 5-, or 6-membered heterocyclic group selected from group a, b, c or d wherein X5 is a group selected from N or CR7 and X6 is a group selected from O, S or NR8; X7 and X8 which may be the same or different is a group selected from N or CR9; X9 is a group selected from O, S or NR8 and X10 is N or CR10; X11, X12 and X13 may be the same or different and selected from a group N or CR11; processes for their preparation, pharmaceutical compositions containing them and their use in medicine.

Benzazepine derivatives for the treatment of neurological disorders

The present invention relates to benzazepine derivatives of formula (I) wherein: R1 represents C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Imidazopyridine derivatives as kinase inhibitors

A compound of the formula and physiologically acceptable salts and or N-oxides thereof wherein, X₁ is N or CR₃; X₂ is N or CR₄; X₃ is N or CR₅; X₄ is N or CR₆. with the proviso that at least one but not more than two of X₁, X₂, X₃ and X₄ represents N. R₁ is a 5-, or 6-membered heterocyclic group selected from group a, b, c or d wherein X₅ is a group selected from N or CR₇ and X₆ is a group selected from O, S or NR₈; X₇ and X₈ which may be the same or different is a group selected from N or CR₉; X₉ is a group selected from O, S or NR₈ and X₁₀ is N or CR₁₀; X₁₁, X₁₂ and X₁₃ may be the same or different and selected from a group N or CR₁₁; processes for their preparation, pharmaceutical ...

PYRAZOLOPYRIDINES AND PYRAZOLOPYRIDAZINES ADN ANTIDIABETICS

The present invention includes compound of formula (I), or a derivative thereof wherein Y is CH or N; R 1 is unsubstituted or substituted alkyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted cycloalkenyl, unsubstituted or substituted aryl, aralkyl wherein the aryl and the alkyl moieties may each independently be unsubstituted or substituted, aralkenyl wherein the aryl, and alkenyl moieties may each independently be unsubstituted or substituted, unsubstituted or substituted heterocyclyl, or heterocyclylalkyl wherein the heterocyclcyl and the alkyl moieties may each inedepently be unsubstituted or substituted; and R 2 is unsubstituted aryl or unsubstituted or substituted or substituted heteroaryl. Additionally the present invention inlcudes a process for preparing such a compound, a pharmaceutical composition containing such a compound, and the use of such a compound in medicine.

Protease inhibitors

This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor.

Novel compounds

The present invention relates to novel pyridone derivatives capable of inhibiting α4 integrin mediated cell adhesion, processes for their preparation, compositions comprising them and their use in the treatment of diseases capable of being modulated by the inhibition of cell adhesion.

Benzazepine derivatives for the treatment of neurological disorders

The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Benzodiazepine bromodomain inhibitor

Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

Benzazepine derivatives as histamine h3 antagonists

The present invention relates to novel benzazepine derivatives of structure (I) having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders. These compounds act as histamine H3 antagonists.

S1P1 AGONISTS COMPRISING A BICYCLIC N-CONTAINING RING

The present invention relates to novel compounds of formula (I) having S1P1 agonist activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

Benzo d!azepine derivatives for the treatment of neurological disorders

The present invention relates to benzazepine derivatives of formula (I) wherein: R1 represents —C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

Compounds

The present invention relates to compounds of formula (I) processes for their preparation, pharmaceutical compositions containing the same and to their use in the treatment of gastrointestinal and other disorders.

Benzodiazepine Bromodomain Inhibitor

Benzodiazepine compounds of formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

COVALENT CONJUGATES OF BET INHIBITORS AND ALPHA AMINO ACID ESTERS

The present invention relates to covalent conjugates of BET inhibitors and alpha amino acid esters, processes for their preparation, compositions containing them, and to their use in the treatment of various disorders in particular inflammatory and autoimmune diseases, such as rheumatoid arthritis; and cancers. 1. A covalent conjugate of a BET inhibitor and an alpha amino acid ester , wherein the ester group of the alpha amino acid ester is hydrolysable by one or more intracellular carboxylesterases to the corresponding carboxylic acid.2. A covalent conjugate according to claim 1 , wherein the alpha amino acid ester is conjugated to the BET inhibitor such that the potency of the covalent conjugate in an in vitro binding assay is no less than 50% of the potency of the unconjugated BET inhibitor in the same assay.3. A covalent conjugate according to claim 2 , wherein the alpha amino acid ester is conjugated to the BET inhibitor such that the potency of the covalent conjugate in an in vitro binding assay is at least as high as that of the unconjugated BET inhibitor in the same assay.5. A covalent conjugate according to claim 4 , wherein Rrepresents hydrogen claim 4 , Calkyl claim 4 , —(CH)cycloalkyl claim 4 , —(CH)heterocycloalkyl claim 4 , or —CRRR claim 4 , and further wherein Ris hydrogen claim 4 , hydroxyl claim 4 , —CHOH claim 4 , —CHCalkyl claim 4 , halo claim 4 , —COOH claim 4 , —CONH claim 4 , 1H-imidazol-4-yl claim 4 , —SH claim 4 , —SeH claim 4 , Calkyl claim 4 , Calkoxy claim 4 , phenyl claim 4 , or 4-hydroxyphenyl wherein said Calkyl or Calkoxy may be optionally substituted with halo claim 4 , hydroxyl claim 4 , —NHC(═NH)NH claim 4 , —NH claim 4 , —COOH claim 4 , —CONH claim 4 , or —SCH claim 4 , and Rand Rare each independently hydrogen or Calkyl claim 4 , and c is 0 claim 4 , 1 or 2.7. A covalent conjugate according to claim 4 , wherein Rrepresents —C(O)OCHRRwherein Ris Calkyl or hydrogen and Ris Calkyl claim 4 , cycloalkyl claim 4 , heterocycloalkyl ...

Pharmaceutical composition

【課題】 α 4 インテグリン介在細胞接着の抑制または阻害が有益である慢性炎症性疾患の予防または治療に有効な医薬組成物を提供する。 【解決手段】 有効成分として下記式(Ｉ)： 【化１】 で示されるα 4 インテグリン介在細胞接着阻害作用を有する化合物またはその薬理学的に許容される誘導体を有効成分とする医薬組成物。 【選択図】 なし

Benzodiazepine bromodomain inhibitor

Alpha-4 integrin mediated cell adhesion inhibitors for the treatment or prevention of inflammatory diseases

The present invention relates to novel compounds of formula (I), processes for their preparation, compositions comprising them and their use in the treatment or prevention of diseases capable of being modulated by the inhibition of cell adhesion.

Protease inhibitors

This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in whi ch inhibition of bone loss is a factor.

Tetrahydrobenzindolone derivatives, their preparation and their use as 5-ht7 receptor antagonists

The invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1 is halogen, C¿1-6?alkyl, hydroxy, C1-6alkoxy, C1-6alkylthio, C1-6alkylsulphinyl, C1-6alkylsulphonyl, amino, mono- or di-C1-6alkylamino, carboxy, carboxamido, hydroxyC1-6alkyl, mono- or di-C1-6alkylaminocarbonyl, sulphonamido, C1-6alkylsulphonylamino, aminoC1-6alkyl, mono- or di-C1-6alkylaminosulphonyl or C1-6alkoxycarbonyl; R?2¿ is hydrogen, C¿1-6?alkyl or arylC1-6alkyl; p is 0, 1, 2 or 3; R?3¿ is hydrogen or C¿1-6?alkyl; n is 2, 3, 4, 5 or 6; A is nitrogen, carbon or CH, ....., is a single bond when A is nitrogen or CH or ..... is a double bond when A is carbon; X is nitrogen or CH; Y is O, S, NH or N-C1-6alkyl, R?4¿ is halogen, C¿1-6?alkyl, cyano, CF3, C3-7cycloalkyl, C1-6alkoxy, hydroxy, amino, mono- or di-C1-6alkylamino, acylamino, nitro, C1-6alkoxycarbonyl, C1-6alkylthio, C1-6alkylsulphinyl, C1-6alkylsulphonyl, sulphamoyl, mono- and di-C1-6alkylsulphamoyl, carbamoyl, mono- and di-C1-6alkylcarbamoyl, C1-6alkylsulphonamido, arylsulphonamido, aryl, arylC1-6alkyl, arylC1-6alkoxy, aryloxy and arylthio; m is 0, 1, 2 or 3, having 5-HT7 antagonist activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS and other disorders.

Alpha-4 integrin mediated cell adhesion inhibitors for the treatment or prevention of inflammatory diseases

The present invention relates to novel compounds of formula (I), processes for their preparation, compositions comprising them and their use in the treatment or prevention of diseases capable of being modulated by the inhibition of cell adhesion.

Oxadiazole derivatives active on sphingosine-1-phosphate (sip)

The present application discloses oxadiazole based compounds of Formula (I) active on sphingosine-1-phosphate (S1P) in particular useful to treat lupus erythematosus. A is phenyl or a 5 or 6-membered heteroaryl ring; R1 is up to two substituents independently selected from halogen, C(1-3)aIkoxy, C(1-3)flyoroalkyl, cyano, optionally substituted phenyl. C(1-3)fluoroalkoxy. C(1-6)alkyl and C(3-6)Cyctoalkyl; R2 is hydrogen, halogen or C(1-4)alkyl; B is a 7 membered saturated ring selected from the following: Formulae (a) (b) (c) R3 is hydrogen or (CH2)1-4MCO2H; R4 is hydrogen or C(1-3)alkyl optionally interrupted by oxygen;

Novel method for preparing beta-alkoxy acrylic acid

A method for preparing compounds of formula (I), wherein R is an optionally substituted alkenyl or alkynyl radical having up to 8 carbon atoms, or an optionally substituted mono- or polycyclic aryl or heteroaryl radical, and R1 and R2 are an alkyl radical having up to 4 carbon atoms. According to the method, a compound of formula (II), wherein X is a halogen atom, is exposed to an organometallic compound of the formula (III): RZ, wherein R has the same meaning as before and Z is a metal or metal derivative. Alternatively, a compound of formula (II'), wherein Z' is a metal or metal derivative, is exposed to a compound of the formula (III'): RX', wherein X' is a nucleophilic reaction leaving group.

Oxadiazole derivatives active on sphingosine-1-phosphate (sip)

Jedinjenje formule (I) ili njegova farmaceutski prihvatljiva so:A je fenil ili piridinil;R1 predstavlja do dva supstituenta nezavisno odabrana od halogena, C(1-3)alkoksi, C(1-3)fluoroalkila, cijano, fenil, C(1-3)fluoroalkoksi, C(1-6)alkil i C(3-6)cikloalkila;R2 je vodonik, halogen ili C(1-4)alkil;B je 7 člani zasićen prsten odabran od slededećih:R3 je vodonik ili (CH2)1-4CO2H;R4 je vodonik;Prijava sadrži još 10 patentnih zahteva. The compound of formula (I) or a pharmaceutically acceptable salt thereof: A is phenyl or pyridinyl, R 1 represents up to two substituents independently selected from halogen, C (1-3) alkoxy, C (1-3) fluoroalkyl, cyano, phenyl, C (1) -3) fluoroalkoxy, C (1-6) alkyl and C (3-6) cycloalkyl, R2 is hydrogen, halogen or C (1-4) alkyl, B is a 7 membered saturated ring selected from the following: R3 is hydrogen or ( CH2) 1-4CO2H, R4 is hydrogen, The application contains 10 more claims.

Compounds

Imidazopyridine derivatives as kinase inhibitors

A compound of the formula: (I) and-physiologically acceptable salts and or N-oxides thereof wherein, X1 is N or CR.3; X2 is N or CR'4; X3 ,is..N or CR5; X4 is N or CR6 with the proviso that at least one but not more than two of X1, X 2, X,3. and X4 represents N. R1 is a 5-, or 6-membered heterocyclic group selected from group a, b, c or d formula: (II) wherein X5 is a group selected from N or CR7: and X6, is a group selected from O, S or NR8; X7 and X8; which maybe the same or, different is a group selected from N or CR9; ; X9, is a group selected from O, S or NR8 and X10 is N or CR10 ; X11 , X12 and X13 may be the same or different and selected from a group N or CR11 ; processes for their preparation, pharmaceutical compositions containing them and their use in medicine.

Benzazepine derivatives for the treatment of neurological disorders

Disclosed herein are benzazepine derivatives of formula (I) pharmacological activity wherein: R1 represents -C3-7 cycloalkyl optionally substituted by C1-3 alkyl; R2, R3 and n are as defined in the specification. Also disclosed are processes for the preparation of these benzazepine derivatives, compositions containing them and their use in the treatment of neurological and psychiatric disorders.

Benzoazepine derivatives for the treatment of neurological disorders

Process for preparing quinolin antibiotic intermediates

The present invention relates to novel pyridone derivatives capable of inhibiting a4 integrin medicated cell adhesion, processes for their preparation, compositions comprising them and their use in the treatment of diseases capable of being modulated by the inhibition of cell adhesion.

Rearrangement of epoxides

Epoxides containing hydroxy groups are rearranged enantioselectively using a chiral base to give allyl alcohols in high enantiomeric excess, e.g. (I) If R3¸H, the reaction also has the effect of generating a chiral tetrasubstituted carbon atom.

Process for preparing quinolin antibiotic intermediates

The present invention relates to novel pyridone derivatives capable of inhibiting a4 integrin medicated cell adhesion, processes for their preparation, compositions comprising them and their use in the treatment of diseases capable of being modulated by the inhibition of cell adhesion.

ACTIVE OXADIAZOL DERIVATIVES ON SPHINGOSINE-1 PHOSPHATE

La presente solicitud describe compuestos a base de oxadiazol de la formula (I), activos sobre 1-fosfato esfingosina (S1P) en particular utiles para tratar lupus eritematoso; A es fenilo o un anillo de heteroarilo de 5 o 6 miembros; R1 es de hasta dos sustituyentes independientemente seleccionados de halogeno

Piperazine derivatives useful for the treatment of gastrointestinal disorders

The invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Ra, Rb, Rc, Rd, Re, Rf and Y are as defined in the specification. The compounds are partial or full agonists at the growth hormone secretagogue (GHS) receptors . Pharmaceutical compositions comprising the compounds, methods of preparing the compounds, uses of the compounds and methods involving the compounds are also provided.

Novel method for preparing beta-alkoxy acrylic acid

Benzodiazepine bromodomain inhibitor

Covalent conjugates of bet inhibitors and alpha amino acid esters

The present invention relates to covalent conjugates of BET inhibitors and alpha amino acid esters, processes for their preparation, compositions containing them, and to their use in the treatment of various disorders in particular inflammatory and autoimmune diseases, such as rheumatoid arthritis;and cancers.

Benzodiazepine derivatives for treating neurological diseases

Benzo[d]azepine derivatives for the treatment of neurological disorders

The present invention relates to a compound which is 6-(3-cyclobutyl-2,3,4,5-tetrahydro-1 H -benzo[ d ]azepin-7-yloxy)- N -methyl-nicotinamide or a pharmaceutically acceptable salt thereof. This compound and its pharmaceutically acceptable salts have affinity for and are antagonists and/or inverse agonists of the histamine H3 receptor. The present invention also relates to processes for the preparation of this benzazepine derivative, to compositions containing it, and to the use of the benzazepine derivative in the treatment of neurological and psychiatric disorders.

Benzodiazepine bromodomain inhibitor

Benzodiazepine compounds of formula (I), and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy, in particular in the treatment of diseases or conditions for which a bromodomain inhibitor is indicated.

Benzodiazepine bromodomain inhibitor

3-substituted indoels or fused pyrroles as antagonists of the chemokine mcp-1 (ccr2b) receptor

Compounds of the formula (I) are antagonists of the chemokine MCP-1 (CCR2B) receptor and are of use in treating in inflammatory conditions with monocyte and/or lymphocyte involvement.

Oxadiazole derivatives active on sphingosine-1-phosphate (sip)

Protease inhibitors

The invention relates to 3-hydroxy- and 3-keto-cyclohetero-substituted leucine compounds that are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor. The 3-hydroxy- or 3-keto-moiety is bonded to a tetrahydrothiophene, tetrahydrothiopyran, tetrahydrofuran or tetrahydropyran ring.

Benzo[d]azepine derivatives for the treatment of neurological disorders

The present invention relates to benzazepine derivatives of formula ( I ) wherein: R1 represents -C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

ACTIVE OXADIAZOL DERIVATIVES ON SPHINGOSINE-1 PHOSPHATE

de la fórmula (l) La presente solicitud describe compuestos a base de oxadiazol activos sobre 1-fosfato esfingosina (S1P) en particular útiles para tratar lupus eritematoso; A es fenilo o un anillo de heteroarilo de 5 ó 6 miembros; R1 es de hasta dos sustituyentes independientemente seleccionados de halógeno, alcoxi deC(l3), fluoroalquilo de C(13), ciano, fenilo opcionalmente sustituido, fluoroalcoxi de C(l3), alquilo de C(l6) y cicloalquilo de C(36); R2 es hidrógeno, halógeno o alquilo de C(l4); B es un anillo saturado de 7 miembros seleccionado de los siguientes: R3 es hidrógeno o (CH2)i..4MCO2H; R4 es hidrógeno o alquilo de C(l3) opcionalmente interrumpido por oxígeno.

Pyrazolopyrimidine derivatives

Benzazepine derivatives as histamine h3 antagonists

The present invention relates to novel benzazepine derivatives of structure (I) having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders. These compounds act as histamine H3 antagonists.

Protease inhibitors

This invention relates to compounds of formula (I) or a pharmaceutically acceptable salt thereof, which are inhibitors of cysteine proteases, particularly cathepsin K, and are useful in the treatment of diseases in which inhibition of bone loss is a factor.

Pyrazolopyridine derivatives

Compounds of formula (I), or a salt thereof, or a solvate thereof, wherein, R 1 is halo, -N=N-heteroaryl, -CO2R5, -NHCH2R6; or -CONR7R8; R2 is H or aryl; R3 is H or aryl, wherein the aryl ring may be optionally substituted by one or more substituents, which may be the same or different, selected from halo; R4 is H; R5 is alkyl; and R6 is H, alkyl, cycloalkyl, aryl or aralkyl; R7 and R8 are selected from H and alkyl; and with the proviso that when R1 is halo, at least one of R2 and/or R3 is aryl; a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds and composition in medicine.

Benzimidazoles and their use as mitogen-activated- and rho-kinase inhibitors

Benzazepine derivatives for the treatment of neurological disorders

Foreliggende oppfinnelse angår et nytt benzazepinderivat som har farmakologisk aktivitet, fremgangsmåte for dets fremstilling, sammensetninger som inneholder det og dets anvendelse ved behandling av neurologiske og psykiatriske forstyrrelser.

Piperazine derivatives as growth hormone secretagogue (ghs) receptor agonists

The present invention relates to compounds of formula (I), processes for their preparation, pharmaceutical compositions containing the same and to their use in the treatment of gastrointestinal and other disorders.

Compounds

Imidazopyridinderivate als kinaseinhibitoren

Benzoädüazepinderivate für die behandlung von neurologischen krankheiten

S1p1 agonists comprising a bicyclic n-containing ring

The present invention relates to novel compounds of formula (I) having S1P1 agonist activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

Benzazepinderivate als histamin-h3-antagonisten

Thiadiazole derivatives and their use for the treatment of disorders mediated by slpl receptors

The present invention relates to novel compounds having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

Neues verfahren zur herstellung von beta- alkoxyacrylsäure

Inhibidores de proteasas vi

Este invento se refiere a compuestos de la fórmula I: (gráfico), en la que: n es 1 ó 2; o una de sus sales farmacéuticamente aceptables, que son inhibidores de cisteína-proteasas, particularmente captesina K, y son útiles en el tratamiento de enfermedades en las que la inhibición de la pérdida de huesos o de la degradación de cartílagos constituye un factor.

Nuevos inhibidores de proteasas, particularmente inhibidores de cisteina y serina proteasas

Esta invención se refiere a compuestos de fórmula (I), (gráfico), o una sal farmacéuticamente aceptable de los mismos, que son inhibidores de cisteína-proteasas, particularmente catepsina K, y son útiles en el tratamiento de enfermedades en las que la inhibición de pérdida de hueso es un factor.

Benzimidazoles and their use as mitogen-activated- and rho-kinase inhibitors

A method of treating an Msk-1 and/or ROCK(1 and 2) mediated disease or condition in a mammal comprising administration of an effective amount of a compounds of the formula (I) and physiologically acceptable salts thereof wherein, R1 is a 5, or 6 membered heterocyclic group selected from group a, b, c or d wherein X1 is a group selected from N or CR7 and X2 is a group selected from O, S or NR8; X3 and X4 which may be the same or different is a group selected from N or CR7; X5 is a group selected from O, S or NR8 and X6 is N or CR7; X7, X8 and X9 may be the same or different and selected from a group N or CR7, pharmaceutical compositions, novel compounds and processes for their preparation.

Inhibidores de proteasas iv

Esta invención se refiere a compuestos de fórmula (I) (gráfico), en la que: R1 es R¿¿ , R¿¿C(O), R¿¿C(S), R¿¿SO2, R¿¿OC(O), R¿¿R1NC(O), o R¿¿OC(O)NR1CH(R6)C(O); R2 es H, alquilo C1-C6 alquenilo C2-C6, Ar-alquilo C0-C6 o Het-alquilo C0-C6; R3 es H, alquilo C1-C6, alquenilo C2-C6, alquinilo C2-C6, cicloalquil C3-C6 alquilo C0-C6, Ar-alquilo C0-C6, o Het-alquilo C0-C6; R4 es H, alquilo C1-C6, alquenilo C2-C6, Ar-alquilo C0-C6 o Het-alquilo C0-C6; R5 en cada caso, es independientemente H, alquilo C1-C6, alquenilo C2-C6, Ar-alquilo C0-C6; R6 es H, alquilo C1-C6, alquenilo C2-C6, cicloalquil C3-C6 alquilo C0-C6, Ar-alquilo C0-C6; o Het-alquilo C0-C6; R¿es H, alquilo C1-C6, alquenilo C2-C6 Ar-alquilo C0-C6 o Het-alquilo C0-C6; R¿¿ el alquilo C1-C6, Ar-alquilo C0-C6, Het-alquilo C0-C6, Ar-alquenilo C2-C6, o Het-alquenilo C2-C6; X es O o S; y n es 1,2 ó 3; o una de sus sales farmacéuticamente aceptables, que son inhibidores de cisteína proteasas, particularmente catepsina K, y son útiles en el tratamiento de enfermedades uno de cuyos factores es la inhibición de pérdida ósea.

Imidazopyridine derivatives as acid pump antagonists

This invention relates to newly identified imidazopyridine compounds of formula (I), to the use of such compounds in therapy and to their production.

Imidazopyridine derivatives as acid pump antagonists

This invention relates to newly identified imidazopyridine compounds of formula (I), to the use of such compounds in therapy and to their production.