Pyrimidinone derivatives and methods of use thereof

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disease, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R, R, R, R, R, R, ring A, ring B, m, n, p, -L-,L-, and L- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'Ris selected from the group consisting of H, lower alkyl, and cyclopropyl.'}3. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '2', 'Ris H.'}4. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '3', 'Ris selected from the group consisting H, alkyl, haloalkyl, and heteroalkyl.'}1413. A pharmaceutical composition comprising at least one compound of any one of - claims 1 , or a tautomer thereof claims 1 , or a stereoisomer of said compound or said tautomer claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , and a pharmaceutically acceptable carrier or diluent.1513 ...

C6-SPIRO IMINOTHIADIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): (structurally represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds, wherein R1, R2, R3, X, Y, s, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed: 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '1', 'Ris methyl;'}{'sup': '2', 'Ris H; and'}{'sup': '3', 'Ris H.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:s is 1;X is —O—; and{'sup': '1Y', 'sub': '2', 'Y is —C(R)—,'}{'sup': '1Y', 'wherein each Ris independently selected from the group consisting of H, lower alkyl, and lower heteroalkyl, wherein said lower alkyl and lower heteroalkyl are each optionally independently unsubstituted or substituted with one or more halogen.'}4. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:s is 0;Y is absent; and{'sup': '1X', 'sub': '2', 'X is selected from the group consisting of —C(R)— and —O—,'}{'sup': '1X', 'wherein each R(when present) is independently selected from the group consisting of H, halogen, lower alkyl, and lower heteroalkyl, wherein said lower alkyl and lower heteroalkyl are each optionally independently unsubstituted or substituted with one or more halogen.'}5. A compound of claim 2 , or a ...

C2-AZASPIRO IMINOTHIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain C2-azaspiro substituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '2', 'each Ris H;'}{'sup': '3', 'each R(when present) is H;'}{'sup': '1A', 'Ris H;'}{'sup': '1B', 'Ris H;'}{'sup': '4', 'sub': '2', 'Ris selected from the group consisting of methyl and —CHF; and'}{'sup': 'N', 'sub': 3', '3', '2', '3', '2', '3', '2', '2', '3', '2', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '2', '2, 'Ris selected from the group consisting of H, —C(O)CH, —C(O)OCH, —C(O)OCHCH, —C(O)OCHCH(CH), —C(O)O-cyclopropyl, —C(O)O—CH-cyclopropyl, —C(O)N(CH), —C(O)NHCH, C(O)-aryl, C(O)-heteroaryl, —S(O)CH, —S(O)-cyclopropyl, —S(O)N(CH), —S(O)NHCH, —S(O)-aryl, —S(O)-heteroaryl, methyl, ethyl, propyl, isopropyl, cyclopropyl, —CH-cyclopropyl, benzyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, oxadiazoyl, isoxazoyl, oxazoyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, —CH-heteroaryl,'}{'sub': 2', '2', '2, 'sup': N', '9, 'wherein said benzyl, phenyl, pyridyl, oxadiazoyl, isoxazoyl, oxazoyl, pyrrolyl, thiazolyl, isothiazolyl, thiadiazolyl, imidazolyl, —CH-heteroaryl, C(O)-aryl, C(O)-heteroaryl, —S(O)-aryl, —S(O)-heteroaryl of Rare each optionally unsubstituted or substituted with R.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:{'sup': 'N', 'sub': 3', '2', '3', '3', '2', '2, ...

Substituted imidazole neuropeptide Y Y5 receptor antagonists

Compounds of the formula Ior a pharmaceutically acceptable salt, solvate or N-oxide thereof, whereinX is =CH- or =N-;Y is H, halogen, trihaloalkyl, alkyl, alkenyl, cycloalkyl, cycloalkyl, SH, -S-alkyl, or -CN.R is alkyl, -CF3, cycloalkyl, heterocycloalkyl, heterocycloalkyl-alkyl, heteroarylalky or adamantyl, or optionally substituted phenyl, phenoxyalkyl, phenylthioalkyl, pyridyl, thienyl, thiazolyl, pyrazinyl, 1,2,5,6-tetrahydropyridine or wherein R10 and R11 are hydrogen, alkyl or together form a cycloalkyl, are disclosed, as well as pharmaceutical compositions and methods of using said compounds in the treatment of eating disorders and diabetes.

FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS

The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I): 3. The compound of claim 1 , wherein Ris C-Calkyl claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.4. The compound of claim 3 , wherein Ris ethyl claim 3 , or a pharmaceutically acceptable salt or prodrug thereof.7. The compound of claim 1 , wherein Ris —N(R) claim 1 , wherein each occurrence of Ris independently selected from H and C-Calkyl claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.8. The compound of claim 7 , wherein Ris —NHCHCH claim 7 , or a pharmaceutically acceptable salt or prodrug thereof.11. A pharmaceutical composition comprising (i) an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and (ii) a pharmaceutically acceptable carrier.12. A method for the inhibition of HIV integrase in a subject in need thereof which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.13. A method for the treatment of infection by HIV or for the treatment claim 1 , prophylaxis claim 1 , or delay in the onset or progression of AIDS in a subject in need thereof claim 1 , which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.14. (canceled)15. (canceled)16. The pharmaceutical composition of claim 11 , further comprising one or more additional therapeutic agents selected from raltegravir claim 11 , lamivudine claim 11 , abacavir claim 11 , ritonavir claim 11 , dolutegravir claim 11 , arunavir claim 11 , atazanavir claim 11 , emtricitabine claim 11 , tenofovir claim 11 , elvitegravir claim 11 , rilpivirine and lopinavir.17. A method for the treatment of infection by HIV or for the treatment claim 11 , prophylaxis claim 11 , or delay in the onset or progression of AIDS in a ...

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

Neuropeptide Y5 receptor antagonists

Compounds of the formula Ior a pharmaceutically acceptable salt thereof, whereina and b are 0-2, provided that the sum is 0-3;X is -O-, -S-, -SO-, -SO2-, -CH(OR8)-, -C(O)-, -C(R23)2-, optionally substituted alkenyl, alkynyl or;R1 is optionally substituted aryl, heteroaryl, substituted amino, alkyl-OC(O)R8, aryloxyalkyl, wherein m is 1-4, or wherein d and e are 0-2;R2, R3, R4 and R5 are H, alkyl, optionally substituted cycloalkyl, halogen, -OR8, -N(R8)2, -CO2R8 or CF3;R6 and R7 are H, alkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkoxy-alkyl, cycloalkyl or cycloalkylalkyl, or R6 and R7, form a 3-7-membered carbocyclic ring, or a 4-7-membered heterocyclic ring;R8 is H, alkyl, cycloalkyl, optionally substituted aryl or heteroaryl;R9 is alkyl, cycloalkyl, optionally substituted aryl or heteroaryl;R11 is H, alkyl or cycloalkyl; andR23 is R8 or halogen; are claimed, as well as additional novel compounds; also claimed are pharmaceutical compositions and methods of using said novel compounds in the ...

Factor XIa inhibitors

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more compounds of Formula (I), and methods for using the compounds of Formula (I) for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination nation with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R, R, R, R, R, R, ring A, ring B, m, n, p, -L-, L-, and L- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed. 119-. (canceled)24. The method of claim 23 , wherein said pharmaceutically acceptable salt is a hydrochloride salt.25. The method of claim 23 , wherein said pharmaceutically acceptable salt is a toluenesulfonate salt.30. The method of claim 29 , wherein said pharmaceutically acceptable salt is a hydrochloride salt.31. The method of claim 29 , wherein said pharmaceutically acceptable salt is a toluenesulfonate salt.36. The method of claim 35 , wherein said pharmaceutically acceptable salt is a hydrochloride salt.37. The method of claim 35 , wherein said pharmaceutically acceptable salt is a toluenesulfonate salt.42. The method of claim 41 , wherein said pharmaceutically acceptable salt is a hydrochloride salt.43. The method of claim 41 , wherein said pharmaceutically acceptable salt is a toluenesulfonate salt. This application claims priority to provisional application U.S. Ser. No. 61/249,685, filed Oct. 8, 2009, incorporated herein by reference.This invention provides certain iminothiadiazine dioxide compounds and compositions comprising these ...

Pyrrolidine-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of W, Z, R1H, R2, R3, R4, ring A, ring B, m, n, p, and -L1- is as defined herein. The novel compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Macrocyclic beta-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Substituted [1,2,4]triazolo[4,3-alpha]quinoxalines as adenosine A2a receptor antagonists

The present invention relates to certain fused tricyclic heteroaryl rings compounds of the Formula (I) (also referred to herein as the "Fused Tricyclic Compounds"), wherein M, Q, U, W, X, Y, Z, R1, R2, and R3, and rings C and D are as herein described. The present invention also provides compositions comprising at least one Fused Tricyclic Compound, and use of such compounds in the treatment of central nervous system diseases or disorders such as Parkinson's disease.

SUBSTITUTED PIPERAZINES AS CB1 ANTAGONISTS

Compounds of Formula (I): 2. A pharmaceutical composition comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'at least one compound according to , or a pharmaceutically acceptable salt thereof.'}3. A composition comprising: at least one compound of , or a pharmaceutically acceptable salt thereof; and at least one additional active agent other than a compound of .4. A composition of claim 3 , wherein said at least one additional active agent is selected from a centrally acting agent and a peripheral acting agent.5. A composition of claim 3 , wherein said at least one additional active agent is selected from a histamine-3 receptor antagonist and a NPY5 antagonist.6. A composition of claim 3 , wherein said at least one additional active agent is selected from a microsomal triglyceride transfer protein (MTP) inhibitor.7. A composition comprising: at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof; and at least one cholesterol lowering compound.8. The composition of claim 7 , wherein said at least one cholesterol lowering compound is at least one sterol absorption inhibitor or at least one 5α-stanol absorption inhibitor.9. The composition of claim 7 , wherein said at least one cholesterol lowering compound is at least one substituted azetidinone compound or substituted β-lactam compound or a pharmaceutically acceptable salt thereof.10. The composition of claim 7 , wherein said at least one cholesterol lowering compound is ezetimibe.11. A method of treating claim 1 , reducing claim 1 , or ameliorating a condition or disease selected from psychic disorders claim 1 , anxiety claim 1 , schizophrenia claim 1 , depression claim 1 , abuse of psychotropes claim 1 , substance abuse claim 1 , substance dependency claim 1 , alcohol dependency claim 1 , nicotine dependency claim 1 , neuropathies claim 1 , migraine claim 1 , stress claim 1 , epilepsy claim 1 , dyskinesias claim 1 , Parkinson's disease claim 1 , amnesia claim 1 , senile dementia ...

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to -amyloid (A) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (A) protein, including Alzheimer's disease, are also disclosed.

FACTOR XIa INHIBITORS

The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

Preparation and use of compounds as protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q is a bond or N(R5); T is a bond, O, C(O); S, N(R5), or C(R6R7); U is a bond or C(R6)(R7) Y is C or N; Z is C or N; ring A, including variables Y and Z, is a three to nine membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, and heteroaryl ring having 0 to 4, preferably 0 to 2, heteroatoms independently selected from the group consisting of O, S, N and N(R), wherein ring A is unsubstituted or substituted with 1 to 5 independently selected R1 moieties and/or oxo when ring A is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl; and R, R1, R2, R3, R4, R5, R6, R6, R7 and R7 are as defined in the specification; pharmaceutical compositions comprising the compounds of formula I and the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases.

SUBSTITUTED AMINOQUINAZOLINE COMPOUNDS AS A2A ANTAGONIST

The present invention is directed to compounds of generic formula (I): or pharmaceutically acceptable salts thereof that are believed to be useful as an A-receptor antagonist. The invention is further directed to methods of treating a patient (preferably a human) for diseases or disorders in which the A-receptor is involved. The invention further involves use of the compounds as an A-receptor antagonist and/or inhibitor for the preparation of a medicament for the treatment and/or prevention of diseases associated with inhibiting the receptor, which includes central nervous system disorders such as Parkinson's disease. The invention is also directed to pharmaceutical compositions which include an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases. 122-. (canceled)24. The compound according to or a pharmaceutically acceptable salt thereof claim 23 , wherein Ris —OCalkyl and Ris hydrogen.25. The compound according to or a pharmaceutically acceptable salt thereof claim 23 , wherein Ris Cheterocyclyl claim 23 , said heterocycle group optionally substituted with 1 to 3 groups of R.26. The compound according to or a pharmaceutically acceptable salt thereof claim 25 , wherein Ris Cheterocyclyl selected from the group consisting unsubstituted or substituted piperidinyl claim 25 , morpholinyl claim 25 , tetrahydropyranyl claim 25 , azabicyclooctyl claim 25 , azabicyloheptyl claim 25 , azepanyl claim 25 , azetidinyl claim 25 , pyrrolidinyl claim 25 , and piperidinone.27. The compound according to or a pharmaceutically acceptable salt thereof claim 23 , wherein Ris optionally substituted Ccycloalkyl.28. The compound according to or a pharmaceutically acceptable salt thereof claim 27 , wherein Ris selected from the group of optionally substituted cyclohexyl claim 27 , cyclobutyl claim ...

PENTAFLUOROSULFUR IMINO HETEROCYCLIC COMPOUNDS AS BACE-1 INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (I): and tautomers thereof, and solvates, prodrugs, esters, and deuterates of said compounds and said tautomers, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R1, R2, R3, R4, R5, R9, R11, ring A, ring B, m, n, p, q, r, -L1-, L2-, and L3- is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (A) protein, including Alzheimers Disease, are also disclosed.

Substituted amide beta secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4 and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Bicyclic heterocycle derivatives and use thereof as GPR119 modulators

The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G-protein coupled receptor (GPCR) such as GPR119 in a patient.

THIOPHENES AS GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE

The present invention relates to compounds of the general formula (I): wherein R, R, R, R, s, and Z are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto. 118-. (canceled)21. A compound of or pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '1', 'claim-text': wherein said phenyl and said naphthyl are substituted with from 1 to 2 groups each independently selected from:', 'halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl; and, 'Ris selected from phenyl and naphthyl,'}{'sup': '2', 'Ris selected from the group consisting of wherein said phenyl and said naphthyl are substituted with from 1 to 2 groups each independently selected from:', 'halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl., 'phenyl and naphthyl,'}22. A compound of or pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': 1', '2, 'claim-text': wherein each of said phenyl and said naphthyl is substituted with from 1 to 2 groups each independently selected from:', 'halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl., 'one of Rand Ris phenyl and the other is naphthyl,'}23. A compound of or pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '1', 'claim-text': wherein said phenyl is substituted with from 1 to 2 groups each independently selected from:', 'halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl; and, 'Ris phenyl,'}{'sup': '2', 'claim-text': wherein said naphthyl is substituted with from 1 to 2 groups each independently selected from:', 'halo, alkyl, haloalkyl, alkoxy, haloalkoxy, and cycloalkyl., 'Ris naphthyl,'}24. A compound of or pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '1', 'claim-text': wherein said naphthyl is substituted with from 1 to 2 groups each independently selected from:', ...

Diazine-fused amidines as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R1B, R2, RA, ring A, RA, m, L1, RL, ring C, RC, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of the variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): 119-. (canceled)21. A compound of claim 20 , or a tautomer thereof claim 20 , or a stereoisomer of said compound or said tautomer claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '1', 'Ris selected from the group consisting of H, lower alkyl, and cyclopropyl.'}22. A compound of claim 20 , or a tautomer thereof claim 20 , or a stereoisomer of said compound or said tautomer claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '2', 'Ris H.'}23. A compound of claim 20 , or a tautomer thereof claim 20 , or a stereoisomer of said compound or said tautomer claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , wherein:{'sup': '3', 'Ris selected from the group consisting H, alkyl, haloalkyl, and heteroalkyl.'}25. A compound of claim 24 , or a tautomer thereof claim 24 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 24 , wherein:ring A is selected from the group consisting of phenyl, pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridazinyl, thiazolyl, oxazolyl, imidazolyl, pyrazolyl, quinazolinyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl, benzothienyl, naphthyl, quinolyl, isoquinolyl, indazolyl, indolyl, and thienopyrazolyl;m is 1 or more;{'sup': 5', '8', '8', '7', '8', '7', '8', '8', '8', '7', '7', '7', '8', '7', '7', '8', '7', '7, 'sub': 5', '5', '2', '2', '2', '2', '2', '2', '2', '2, 'and each Rgroup is independently selected from the group consisting of halogen, —CN, —SF, —OSF, —N(R), —NRC(O)R, —NRS(O)R, —NRC(O)N(R), —NRC(O)OR, —C(O)R, —C(O)R, —C(O)N(R), —S(O)R, —S(O)R, —S(O)N(R), —OR, —SR, lower alkyl, lower haloalkyl, lower heteroalkyl, lower alkynyl, cycloalkyl, heteroaryl, and heterocycloalkyl.'}26. A compound of claim 24 , or a tautomer thereof claim 24 , or a pharmaceutically acceptable salt of said ...

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Fused Tricyclic Heterocyclic Compounds Useful For Treating HIV Infection

The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, m, R, R, R, R, R, R, Rand Rare as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocycle Derivative, and methods of using the Fused Tricyclic Heterocycle Derivatives for treating or preventing HIV infection in a subject. 2. The compound of claim 1 , wherein X is —NHC(O)— claim 1 , or a pharmaceutically acceptable salt thereof.3. The compound of claim 1 , wherein X is 5 or 6-membered monocyclic heteroaryl claim 1 , or a pharmaceutically acceptable salt thereof.5. The compound of claim 1 , wherein Y is CH claim 1 , or a pharmaceutically acceptable salt thereof.7. The compound of claim 1 , wherein Ris phenyl claim 1 , which is substituted by 1 to 3 halo groups claim 1 , which can be the same or different claim 1 , or a pharmaceutically acceptable salt thereof.8. The compound of claim 7 , wherein Ris 2 claim 7 ,4-difluorophenyl claim 7 , 3-chloro-2 claim 7 ,4-difluorophenyl or 3-chloro-2-fluorophenyl claim 7 , or a pharmaceutically acceptable salt thereof.9. The compound of claim 1 , wherein the group -A-B— is —CH—O— claim 1 , or a pharmaceutically acceptable salt thereof.10. The compound of claim 1 , wherein Ris —(C-Calkylene)-O—(C-Calkyl) claim 1 , or a pharmaceutically acceptable salt thereof.11. The compound of claim 1 , wherein Ris C-Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.12. The compound of claim 1 , wherein Ris C-Calkyl claim 1 , or a pharmaceutically acceptable salt thereof.13. The compound of claim 12 , wherein Ris methyl claim 12 , or a pharmaceutically acceptable salt thereof.15. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.16. A method for the inhibition of HIV integrase ...

Neuropeptide Y Y5 receptor antagonists

The present invention discloses compounds which, are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS

The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I): 3. The compound of or , wherein Ris C-Calkyl.4. The compound of claim 3 , wherein Ris ethyl.7. The compound of any of to claim 3 , wherein Ris —N(R) claim 3 , wherein each occurrence of Ris independently selected from H and C-Calkyl.8. The compound of claim 7 , wherein Ris —NHCHCH.10. A compound being any one of the compounds numbered 1-75 in the above specification claim 7 , or a pharmaceutically acceptable salt or prodrug thereof.11. A pharmaceutical composition comprising (i) an effective amount of a compound according to any one of to claim 7 , or a pharmaceutically acceptable salt or prodrug thereof claim 7 , and (ii) a pharmaceutically acceptable carrier.12. A method for the inhibition of HIV integrase in a subject in need thereof which comprises administering to the subject an effective amount of the compound according to any one of to claim 7 , or a pharmaceutically acceptable salt or prodrug thereof.13. A method for the treatment of infection by HIV or for the treatment claim 7 , prophylaxis claim 7 , or delay in the onset or progression of AIDS in a subject in need thereof claim 7 , which comprises administering to the subject an effective amount of the compound according to any one of to claim 7 , or a pharmaceutically acceptable salt or prodrug thereof.14. A compound according to any one of to claim 7 , or a pharmaceutically acceptable salt or prodrug thereof claim 7 , for use in therapy.15. A compound according to any one of to claim 7 , or a pharmaceutically acceptable salt or prodrug thereof claim 7 , for use in the preparation of a medicament for the inhibition of HIV integrase claim 7 , for the treatment or prophylaxis of infection by HIV claim 7 , or for the treatment claim 7 , prophylaxis claim 7 , or delay in the onset or progression of AIDS in a subject in need thereof.16. The pharmaceutical composition of claim 11 , further comprising one or more additional ...

Substituted imidazole neuropeptide Y Y5 receptor antagonists

Compounds of the formula Ior a pharmaceutically acceptable salt, solvate or N-oxide thereof, whereinX is =CH- or =N-;Y is H, halogen, trihaloalkyl, alkyl, alkenyl, cycloalkyl, cycloalkyl, SH, -S-alkyl, or -CN.R is alkyl, -CF3, cycloalkyl, heterocycloalkyl, heterocycloalkyl-alkyl, heteroarylalky or adamantyl, or optionally substituted phenyl, phenoxyalkyl, phenylthioalkyl, pyridyl, thienyl, thiazolyl, pyrazinyl, 1,2,5,6-tetrahydropyridine orwherein R<10 and R<11 are hydrogen, alkyl or together form a cycloalkyl, are disclosed, as well as pharmaceutical compositions and methods of using said compounds in the treatment of eating disorders and diabetes. ...

PYRROLIDINE-FUSED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of W, Z, R, R, R, R, ring A, ring B, m, n, p, and -L- is as defined herein. The novel compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed. 3. A compound of claim 2 , or a stereoisomer of said compound claim 2 , or a pharmaceutically acceptable salt of said compound or said stereoisomer claim 2 , wherein:{'sup': '6', 'Ris lower alkyl.'}5. A compound of claim 4 , or a stereoisomer of said compound claim 4 , or a pharmaceutically acceptable salt of said compound or said stereoisomer claim 4 , wherein:{'sup': '8A', 'Ris selected from lower alkyl, lower alkoxy, lower haloalkyl, lower heteroalkyl, cyclopropyl, and -loweralkyl-cyclopropyl;'}{'sup': '8B', 'Ris selected from H, fluorine and chlorine; and'}{'sup': '8C', 'Ris selected from lower alkyl, lower alkoxy, lower haloalkyl, lower heteroalkyl, cyclopropyl, and -loweralkyl-cyclopropyl.'}7. A compound according to claim 6 , or a stereoisomer of said compound claim 6 , or a pharmaceutically acceptable salt of said compound or said stereoisomer claim 6 , wherein:n is 0;ring A is phenyl;m is 0 to 4; and{'sup': '2', 'sub': 5', '2', '3', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3', '3', '2, 'each Rgroup (when present) is independently selected from the group consisting of halogen, —CN, —SF, —NH, —NHCH, —N(CH), —OCH, —OCHCH, —O-cyclopropyl, ...

Preparation and Use of Cyclic Sulfonamide Derivatives as PAR-1 Receptor Antagonists

The present invention relates to cyclic sulfonamide derivatives of Formula (I) or a pharmaceutically acceptable salt thereof.

Amino-quinoxaline and amino-quinoline compounds for use as adenosine A2a receptor antagonists

Compounds of the Formula (I), where W represents CH or N; and Q represents CN, C(NOH)NH2, CONHR1 or various herein described heterocyclic radicals; as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

MACROCYCLIC BETA-SECRETASE INHIBITORS

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of -secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R, R, R, R, R, R, ring A, ring B, m, n, p, -L-, L-, and L- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination nation with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed. 119-. (canceled)21. The method of claim 20 , wherein:{'sup': '1', 'Ris selected from the group consisting of H, lower alkyl, and cyclopropyl.'}22. The method of claim 20 , wherein:{'sup': '2', 'Ris H.'}23. The method of claim 20 , wherein:{'sup': '3', 'Ris selected from the group consisting H, alkyl, haloalkyl, and heteroalkyl.'}33. The method according to claim 20 , wherein said Aβ pathology is selected from Alzheimer's disease claim 20 , Down's syndrome claim 20 , Parkinson's disease claim 20 , memory loss claim 20 , memory loss associated with Alzheimer's disease claim 20 , memory loss associated with Parkinson's disease claim 20 , attention deficit symptoms claim 20 , attention deficit symptoms associated with Alzheimer's disease claim 20 , Parkinson's disease claim 20 , and/or Down's syndrome claim 20 , dementia claim 20 , stroke claim 20 , microgliosis and brain inflammation claim 20 , pre-senile dementia claim 20 , senile dementia claim 20 , dementia associated with Alzheimer's disease claim 20 , Parkinson's disease claim 20 , and/or ...

C6-azaspiro iminothiadiazine dioxides as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C2-ring-substituted thiadiazine compounds, including compounds Formula (I): (structure represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1, R4, ring A, RA, m, -L1-, RL, and ring C are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Iminothiadiazine dioxide compounds as brace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to -amyloid (A) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (A) protein, including Alzheimer's disease, are also disclosed.

Iminothiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to -amyloid (A) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (A) protein, including Alzheimers disease, are also disclosed.

6,7-dihydro-5H-pyrrolo[3,4-B]pyridin-5-one allosteric modulators of the M4 muscarinic acetylcholine receptor

The present invention is directed to 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula I are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

BICYCLIC HETEROCYCLE DERIVATIVES AND USE THEREOF AS GPR119 MODULATORS

The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G-protein coupled receptor (GPCR) such as GPR119 in a patient.

SUBSTITUTED AMIDE BETA SECRETASE INHIBITORS

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4 and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

PYRIMIDINONE DERIVATIVES AND METHODS OF USE THEREOF

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disease, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

AMINO-QUINOXALINE AND AMINO-QUINOLINE COMPOUNDS FOR USE AS ADENOSINE A2a RECEPTOR ANTAGONISTS

Compounds of the Formula (I), where W represents CH or N; and Q represents —CN, —C(═NOH)NH2, —CONHR1 or various herein described heterocyclic radicals; as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof. Care adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

PYRIMIDINONE DERIVATIVES AND METHODS OF USE THEREOF

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of G protein-coupled receptor 119 (GPR119) in a patient.

Substituted urea neuropeptide Y Y5 Receptor antagonists

A novel class of compounds such as antagonists of the neuropeptide Y Y5 receptor, methods of making such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention or amelioration of one or more diseases associated with the neuropeptide Y Y5 receptor are disclosed.

Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (I): and tautomers thereof, and solvates, prodrugs, esters, and deuterates of said compounds and said tautomers, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R1, R2, R3, R4, R5, R9, R11, ring A, ring B, m, n, p, q, r, -L1-, L2-, and L3- is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Abeta) protein, including Alzheimers Disease, are also disclosed.

FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS

The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I): 3. The compound of claim 1 , wherein Ris C-Calkyl claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.4. The compound of claim 3 , wherein Ris ethyl claim 3 , or a pharmaceutically acceptable salt or prodrug thereof.7. The compound of claim 1 , wherein Ris —N(R) claim 1 , wherein each occurrence of Ris independently selected from H and C-Calkyl claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.8. The compound of claim 7 , wherein Ris —NHCHCH claim 7 , or a pharmaceutically acceptable salt or prodrug thereof.11. A pharmaceutical composition comprising (i) an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof claim 1 , and (ii) a pharmaceutically acceptable carrier.12. A method for the inhibition of HIV integrase in a subject in need thereof which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.13. A method for the treatment of infection by HIV or for the treatment claim 1 , prophylaxis claim 1 , or delay in the onset or progression of AIDS in a subject in need thereof claim 1 , which comprises administering to the subject an effective amount of the compound according to claim 1 , or a pharmaceutically acceptable salt or prodrug thereof.14. (canceled)15. (canceled)16. The pharmaceutical composition of claim 11 , further comprising one or more additional therapeutic agents selected from raltegravir claim 11 , lamivudine claim 11 , abacavir claim 11 , ritonavir claim 11 , dolutegravir claim 11 , arunavir claim 11 , atazanavir claim 11 , emtricitabine claim 11 , tenofovir claim 11 , elvitegravir claim 11 , rilpivirine and lopinavir.17. A method for the treatment of infection by HIV or for the treatment claim 11 , prophylaxis claim 11 , or delay in the onset or progression of AIDS in a ...

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I 3. A compound of wherein U is a bond or —C(R)(R)—.4. A compound of wherein U is a bond.5. A compound of wherein U is —C(R)(R)—.6. A compound of wherein Ris H.7. A compound of wherein R claim 1 , R claim 1 , Rand Rare independently selected from the group consisting of alkyl claim 1 , cycloalkyl claim 1 , cycloalkylalkyl claim 1 , heterocycloalkyl claim 1 , heterocycloalkylalkyl claim 1 , aryl claim 1 , arylalkyl claim 1 , heteroaryl claim 1 , heteroarylalkyl claim 1 , halo claim 1 , —CH—O—Si(R)(R)(R) claim 1 , —SH claim 1 , —CN claim 1 , —OR claim 1 , —C(O)R claim 1 , —C(O)OR claim 1 , —C(O)N(R)(R) claim 1 , —SR claim 1 , —S(O)N(R)(R) claim 1 , —S(O)N(R)(R) claim 1 , —N(R)(R) claim 1 , —N(R)C(O)R claim 1 , —N(R)S(O)R claim 1 , —N(R)C(O)N(R)(R) claim 1 , —N(R)C(O)ORand —C(═NOH)R.8. A compound of wherein R claim 1 , R claim 1 , Rand Rare selected from the group consisting of aryl claim 1 , heteroaryl claim 1 , heteroarylalkyl claim 1 , arylalkyl claim 1 , cycloalkyl claim 1 , heterocycloalkyl claim 1 , heterocycloalkylalkyl claim 1 , alkyl and cycloalkylalkyl.11. (canceled)1320-. (canceled)23. A compound of wherein U is a bond or —C(R)(R)—.24. A compound of wherein U is a bond.25. A compound of wherein U is —C(R)(R)—.26. A compound of wherein Ris H.27. A compound of wherein R claim 21 , R claim 21 , Rand Rare independently selected from the group consisting of alkyl claim 21 , cycloalkyl claim 21 , cycloalkylalkyl claim 21 , heterocycloalkyl claim 21 , heterocycloalkylalkyl claim 21 , aryl claim 21 , arylalkyl claim 21 , heteroaryl claim 21 , heteroarylalkyl claim 21 , halo claim 21 , —CH—O—Si(R)(R)(R) claim 21 , —SH claim 21 , —CN claim 21 , —OR claim 21 , —C(O)R claim 21 , —C(O)OR claim 21 , —C(O)N(R)(R) claim 21 , —SR claim 21 , —S(O)N(R)(R) claim 21 , —S(O)N(R)(R) claim 21 , —N(R)(R) claim 21 , —N(R)C(O)R claim 21 , —N(R)S(O)R claim 21 , —N(R)C(O)N(R)(R) claim 21 , —N(R)C(O)ORand —C(═NOH)R.28. A compound of wherein R claim ...

Neuropeptide Y Y5 receptor antagonists

The present invention discloses compounds which, are receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

C5-C6 OXACYCLIC-FUSED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula: (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of ring A, ring B, ring C, R, R, R, m, n, p, and -L- is as defined herein. The novel compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , said tautomer claim 1 , or said stereoisomer claim 1 , wherein:{'sup': '4', 'Ris H.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a stereoisomer of said compound or said tautomer claim 2 , or a pharmaceutically acceptable salt of said compound claim 2 , said tautomer claim 2 , or said stereoisomer claim 2 , wherein:{'sup': '1H', 'sub': 2', '2', '3', '2', '2, 'each Ris selected from the group consisting of H, methyl, cyclopropyl, —CH-cyclopropyl, —CHOCH, trifluoromethyl, —CHF, and —CHF.'}4. A compound of claim 3 , or a tautomer thereof claim 3 , or a stereoisomer of said compound or said tautomer claim 3 , or a pharmaceutically acceptable salt of said compound claim 3 , said tautomer claim 3 , or said stereoisomer claim 3 , wherein:n is 1;ring A is selected from the group consisting of phenyl, thienyl, and pyridyl;m is 0 or 1;{'sup': '2', 'sub': 5', '3', '3', '2', '3', '2', '3', '3', '2', '3', '3', '2', '3', '2', '3', '3', '2, 'each Rgroup (when present) is independently selected from the group consisting of halogen, —CN, —SF, —NHCH, —N(CH), —OCH, ...

Substituted Piperazines as CB1 Antagonists

Compounds of Formula (I): or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.

NOVEL PYRROLIDINES AS GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE

The present invention relates to compounds of the general formula: (I) wherein ring B, R, R, R, Z, and Lare selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto. 117-. (canceled)23. A compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein Ris selected from the group consisting of H and methyl.24. A compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein Ris naphthyl claim 22 ,wherein said naphthyl is substituted with from 1 to 3 groups each independently selected from:{'sub': 3', '3', '3, '—Cl, —F, —CF, —O—CH, and —OCF.'}26. A compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein Z is selected from the group consisting of —(CH)—(CH(CH))—C(O)OH claim 22 , —(CH)—(CH) —(CH)—C(O)OH claim 22 , —(CH)—C(CH)—C(O)OH claim 22 , —(CH)—C(CH)(OH)—C(O)OH claim 22 , —CH—CH—C(O)OH claim 22 , —CH—CH(OH)—C(O)OH claim 22 , —CH(CH)—CH—C(O)OH claim 22 , —CH—CH(F)—C(O)OH claim 22 , —CH—CF—C(O)OH claim 22 , —CH(CH)—CF—C(O)OH claim 22 , and —CH—CH—CF—C(O)OH.27. A compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein:{'sup': '3', 'Ris H; and'}{'sub': 2', '3', '2', '2', '2', '2', '3', '2', '2', '3', '2', '2', '2', '3', '2', '2', '2', '2', '3', '2', '2', '2', '2, 'Z is selected from the group consisting of —(CH)—(CH(CH))—C(O)OH, —(CH)—(CH)—(CH)—C(O)OH, —(CH)—C(CH)—C(O)OH, —(CH)—C(CH)(OH)—C(O)OH, —CH—CH—C(O)OH, —CH—CH(OH)—C(O)OH, —CH(CH)—CH—C(O)OH, —CH—CH(F)—C(O)OH, —CH—CF—C(O)OH, —CH(CH)—CF—C(O)OH, and —CH—CH—CF—C(O)OH.'}28. A compound of claim 22 , or a pharmaceutically acceptable salt thereof claim 22 , wherein Z is —CH—CH—C(O)OH.30. A pharmaceutical composition comprising a compound of claim 18 , or a pharmaceutically acceptable salt thereof claim 18 , and ...

PROCESSES FOR THE PREPARATION OF A BACE INHIBITOR

This invention provides processes for the preparation of verubecestat (Compound of Formula (I)), a potent inhibitor of BACE-1 and BACE-2. In addition, the invention provides certain synthetic intermediates which are useful, among other things, for the preparation of the Compound of Formula (I). 2. The process of claim 1 , wherein the cyanating agent is selected from the group consisting of cyanogen claim 1 , cyanogen bromide claim 1 , cyanogen fluoride claim 1 , cyanogen chloride claim 1 , cyanogen iodide claim 1 , 2-methoxyphenyl cyanate claim 1 , 4-methoxyphenyl cyanate claim 1 , 4-phenylphenyl cyanate claim 1 , and bisphenol A cyanate.3. The process of claim 2 , wherein the cyanating agent is cyanogen bromide.7. The process of claim 6 , wherein the copper or palladium reagent is selected from the group consisting of CuI claim 6 , CuI-TBAI claim 6 , CuBr claim 6 , CuPF(MeCN) claim 6 , CuBr claim 6 , [Cu(OTf)]-tol claim 6 , CuCl claim 6 , Cu metal claim 6 , CuO claim 6 , Cu(OAc) claim 6 , (aminobiphenyl)PdOMs dimer claim 6 , and (aminobiphenyl)PdCl dimer.8. The process of claim 6 , wherein the ligand is selected from the group consist of N claim 6 ,N′-dimethyl diaminocyclohexane claim 6 , diaminocyclohexane claim 6 , tBuBrettphos claim 6 , DMEDA claim 6 , Xphos claim 6 , RuPhos claim 6 , Sphos claim 6 , water-soluble Sphos claim 6 , tBuXPhos claim 6 , Rockphos claim 6 , Brettphos claim 6 , AdBrettphos claim 6 , Qphos claim 6 , MorDalphos claim 6 , Amphos claim 6 , CataCXiumA claim 6 , tBuP claim 6 , CyP claim 6 , MeCgPPh claim 6 , o-tolP claim 6 , PPh claim 6 , BINAP claim 6 , dppf claim 6 , dtbpf claim 6 , Josiphos SL-J009 claim 6 , Johnphos claim 6 , Xantphos claim 6 , and NiXantphos.9. The process of claim 6 , wherein the Brønsted base is selected from the group consisting of potassium carbonate claim 6 , potassium phosphate claim 6 , cesium carbonate claim 6 , and potassium bicarbonate.12. The process of wherein Ris tert-butyl.13. The process of claim 12 , ...

Neuropeptide Y Y5 receptor antagonists

The present invention discloses compounds which, are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

COMPOUNDS INHIBITING LEUCINE-RICH REPEAT KINASE ENZYME ACTIVITY

The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R9, and A are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H and Ris selected from the group consisting of H and halo.3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof claim 2 , wherein A is CH.4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof claim 3 , wherein A is N.5. The compound of wherein Ris selected from the group consisting of H claim 2 , —(C)alkyl claim 2 , —(C)alkenyl claim 2 , —O(C)alkyl claim 2 , heteroaryl claim 2 , —(C)cycloalkyl claim 2 , and —(C)cycloalkenyl claim 2 , wherein each said heteroaryl claim 2 , —(C)cycloalkyl claim 2 , and —(C)cycloalkenyl claim 2 , is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of alkyl claim 2 , alkoxy claim 2 , halo claim 2 , cyano claim 2 , hydroxyl claim 2 , and oxo.6. The compound of wherein Rand Rare taken together with the atoms to which they are shown attached to form a morpholinyl group claim 5 , a piperazinyl group claim 5 , a piperadinyl group claim 5 , a 5 claim 5 ,6 claim 5 ,7 claim 5 ,8-tetrahydroimidazo[1 claim 5 ,2-a]pyrazinyl claim 5 , a 5 claim 5 ,6 claim 5 ,7 claim 5 ,8-tetrahydro-[1 claim 5 ,2 claim 5 ,4]triazolo[4 claim 5 ,3-a]pyrazinyl claim 5 , an azetidinyl group claim 5 , or a pyrrolidinyl group claim 5 , wherein each said group is optionally substituted with from 1 to 4 ...

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (a) and include tautomers, solvates, prodrugs, esters, and deuterates thereof, and pharmaceutically acceptable salts of said compounds, tautomers, solvates, prodrugs, esters, and deuterates, wherein each of R, R, R, R, R, R, ring A, ring B, ring C, m, n, p, q, -L-, -L-, L-, and L- is selected independently and as defined herein. The compounds of the invention have, surprisingly and advantageously, improved solution stability. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed. 3. A compound of claim 1 , or a tautomer or stereoisomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , tautomer claim 1 , or stereoisomer claim 1 , wherein:{'sup': '1', 'Ris selected from the group consisting of H, lower alkyl, and cyclopropyl.'}4. A compound of claim 1 , or a tautomer or stereoisomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , tautomer claim 1 , or stereoisomer claim 1 , wherein:{'sup': '2', 'Ris H.'}5. A compound of claim 1 , or a tautomer or stereoisomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , tautomer claim 1 , or stereoisomer claim 1 , wherein:{'sub': '2', '-L- is absent or a -alkyl- group; and'}{'sup': '3', 'Ris selected from the group consisting H, alkyl, haloalkyl, heteroalkyl, cycloalkyl, and cycloalkylalkyl-.'}7. A compound of claim 6 , or a tautomer or stereoisomer thereof claim 6 , or a pharmaceutically acceptable salt of said compound claim 6 , tautomer claim 6 , or stereoisomer claim 6 , wherein:{'sub': '1', '-L- is absent or a divalent -alkyl- group;'}m is 0 or more and ring A is ...

THIOPHENYL-SUBSTITUTED 2-IMINO-3-METHYL PYRROLO PYRIMIDINONE COMPOUNDS AS BACE-1 INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides provides certain thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds (or tautomers or a pharmaceutically acceptable salts thereof) having the structural Formula (III): wherein R2, R3, R4, R5, R6, R7, R8, and R9 are each selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds, and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's Disease, are also disclosed.

Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment

Substituted cyclopropyl compounds of the formula I and the pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the g-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included. Another aspect of the invention that is of interest relates to compounds of formula 1a.

Pyrrolidines as glucagon receptor antagonists, compositions, and methods for their use

The present invention relates to compounds of the general formula: (I) wherein ring B, R1, R2, R3, Z, and L1 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

C5-C6 oxacyclic-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of ring A, ring B, ring C, R 2 , R 3 , R 4 , m, n, p, and -L 1 - is as defined herein. The novel compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 5-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

PREPARATION AND USE OF COMPOUNDS AS PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Q is a bond or —N(R 5 )—; T is a bond, —O—, —C(O)—; S, —N(R 5 )—, or —C(R 6′ R 7′ ); U is a bond or —C(R 6 )(R 7 )— Y is C or N; Z is C or N; ring A, including variables Y and Z, is a three to nine membered cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, and heteroaryl ring having 0 to 4, preferably 0 to 2, heteroatoms independently selected from the group consisting of O, S, N and —N(R)—, wherein ring A is unsubstituted or substituted with 1 to 5 independently selected R 1 moieties and/or oxo when ring A is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl; and R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 6 , R 7 and R 7′ are as defined in the specification; pharmaceutical compositions comprising the compounds of formula I and the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

5-substituted iminothiazines and their mono- and dioxides as BACE inhibitors, compositions, and their use

The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed.

1,2,4-TRIAZOLO[4,3-c]PYRIMIDIN-3-ONE AND PYRAZOLO[4,3-e]-1,2,4-TRIAZOLO[4,3-c]PYRIMIDIN-3-ONE COMPOUNDS FOR USE AS ADENOSINE A2a RECEPTOR ANTAGONISTS

Compounds of the Formula I wherein R1and R2together with the carbon atoms to which they are bonded optionally form a further heteroaromatic ring of the formula (II) as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS

... and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.

Xanthine phosphodiesterase V inhibitors

A xanthine phosphodiesterase V inhibitor having the formula (I), with the variables defined herein, which is especially useful for treating male (erectile) and female sexual dysfunction and other physiological disorders: For example, a representative compound of the invention is: ...

PENTAFLUOROSULFUR IMINO HETEROCYCLIC COMPOUNDS AS BACE-1 INHIBITORS, COMPOSITIONS AND THEIR USE

In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula (a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed. 3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '1', 'Ris selected from the group consisting of H, lower alkyl, and cyclopropyl.'}4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '2', 'Ris H.'}5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sub': '2', '-L- is a bond or a -alkyl- group; and'}{'sup': '3', 'Ris selected from the group consisting H, alkyl, haloalkyl, heteroalkyl, cycloalkyl, and cycloalkylalkyl-.'}7. A compound of claim 6 , or a pharmaceutically acceptable salt thereof claim 6 , wherein:{'sub': '1', '-L- is a bond or a divalent -alkyl- group;'}m is 0 or more;s is 0, 1, or 2;ring A is selected from the group consisting of phenyl, pyridyl, pyrazinyl, pyrazolyl, furanyl, thienyl, pyrimidinyl, pyridazinyl, thiazolyl, and oxazolyl;{'sup': 4', '8', '8', '7', '8', '7, 'sub': 2', '2', '2, 'each R(when present) is independently selected from the group consisting of halo, —CN, —NO, —N(R), —NRC(O)R, —C(O)N(R), —OR, alkyl, haloalkyl, heteroalkyl, and alkynyl;'}{'sub': 3', '2, '-L- is a bond or a divalent —CH— group;'}n is 0 or more;r is 0, 1, or 2;ring B is selected from the group consisting of phenyl, benzoxazolyl, benzofuranyl, benzimidazolyl, benzisoxazolyl, pyridyl, pyrazinyl, furanyl, thienyl, pyrimidinyl, pyridazinyl, ...

C6-spiro iminothiadiazine dioxides as BACE inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C5-spiro iminothiadiazine dioxide compounds, including compounds Formula (I): (structurally represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds, wherein R1, R2, R3, X, Y, s, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O) 2 —, —C(═O)—, —O—, —C(R 6 )(R 7 )—, —N(R 5 )— or —C(═N(R 5 ))—; X is —O—, —N(R 5 )— or —C(R 6 )(R 7 )—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O) 2 —, —C(═O)— or —C(═NR 5 )—; U is a bond, —S(O)—, —S(O) 2 —, —C(O)—, —O—, —P(O)(OR 15 )—, —C(═NR 5 )—, —(C(R 6 )(R 7 )) b — or —N(R 5 )—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, U is not —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—; provided that when X is —N(R 5 )— and W is —S(O)—, —S(O) 2 —, —O—, or —N(R 5 )—, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Pentafluorosulfur imino heterocyclic compounds as BACE-1 inhibitors, compositions and their use

In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula (a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Abeta) protein, including Alzheimers Disease, are also disclosed.

Compounds inhibiting leucine-rich repeat kinase enzyme activity

The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R9, and A are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, C(S), S(O), S(O)2, C(O), O, C(R6)(R7), N(R5) or C(N(R5)); X is O, N(R5) or C(R6)(R7); provided that when X is O, U is not O, S(O), S(O)2, C(O) or C(NR5); U is a bond, S(O), S(O)2, C(O), O, P(O)(OR15), C(NR5), (C(R6)(R7))b or N(R5); wherein b is 1 or 2; provided that when W is S(O), S(O)2, O, or N(R5), U is not S(O), S(O)2, O, or N(R5); provided that when X is N(R5) and W is S(O), S(O)2, O, or N(R5), then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula 1 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

NOVEL SPIRO IMIDAZOLONES AS GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE

The present invention relates to compounds of the general formula: wherein ring A, ring B, R1, R3, Z, L1, and L2 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and to methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto. 2. A composition comprising a compound according to and a pharmaceutically acceptable carrier.3. A composition of claim 1 , further comprising one or more antidiabetic agents other than a compound of .4. A composition of claim 3 , further comprising at least one pharmaceutically acceptable carrier.5. A composition of claim 3 , further comprising at least one additional therapeutic agent selected from the group consisting of: DPP-IV inhibitor claim 3 , an insulin sensitizer claim 3 , insulin claim 3 , an insulin mimetic claim 3 , an insulin secretagogue claim 3 , a GLP-1 mimetic claim 3 , a glucosidase inhibitor claim 3 , an alpha glucosidase inhibitor claim 3 , a glucagon receptor antagonist other than a compound of claim 3 , glucophage claim 3 , glucophage XR claim 3 , an antihypertensive agent claim 3 , a meglitinide claim 3 , an alpha-glucosidase inhibitor claim 3 , amlintide claim 3 , pramlintide claim 3 , exendin claim 3 , a histamine Hreceptor antagonist claim 3 , dapagliflozin claim 3 , sergliflozin claim 3 , AVE2268 (Sanofi-Aventis) and T-1095 (Tanabe Seiyaku) claim 3 , a cholesterol lowering agent claim 3 , a PACAP claim 3 , a PACAP mimetic claim 3 , a PACAP receptor 3 agonist claim 3 , a PPAR delta agonist claim 3 , an antiobesity agent claim 3 , an ileal bile acid transporter inhibitor claim 3 , an NSAID claim 3 , and a CB1 receptor antagonist claim 3 , and a CB1 receptor inverse agonist.6. A method for treating type 2 diabetes mellitus in a patient in need thereof claim 1 , comprising administering to said patient an effective amount of at least one compound according to .7. A ...

PHENYL-SUBSTITUTED 2-IMINO-3-METHYL PYRROLO PYRIMIDINONE COMPOUNDS AS BACE-1 INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds Formula (II): and include tautomers, steroisomers, or pharmaceutically acceptable salts or solvates of said compounds, stereoisomers, or said tautomers, wherein R2, R3, R4, R5, R6, R7, R8, and R9 are each selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds, and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's Disease, are also disclosed.

HETEROCYCLIC ASPARTYL PROTEASE INHIBITORS

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Polycyclic guanine derivative phosphodiesterase V inhibitors

A compound having the formula (Ia) or (b), salt or solvate thereof, with the variables as defined herein, which can inhibit selectively phosphodiesterase V and can be useful for treating sexual dysfunction and other physiological disorders, symptoms and diseases: ...

Substituted piperazines as CB1 antagonists

Compounds of Formula (I): or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB 1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.

Phenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as BACE-1 inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds Formula (II): and include tautomers, steroisomers, or pharmaceutically acceptable salts or solvates of said compounds, stereoisomers, or said tautomers, wherein R2, R3, R4, R5, R6, R7, R8, and R9 are each selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds, and methods for their preparation and use in treating pathologies associated with amyloid beta (Abeta) protein, including Alzheimer's Disease, are also disclosed.

2-SPIRO-SUBSTITUTED IMINOTHIAZINES AND THEIR MONO-AND DIOXIDES AS BACE INHIBITORS, COMPOSITIONS AND THEIR USE

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of the variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Thiophenes as glucagon receptor antagonists, compositions, and methods for their use

The present invention relates to compounds of the general formula: wherein R1, R2, R3, R5, s, and Z are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

DIAZINE-FUSED AMIDINES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R, R, R, R, ring A, R, m, L, R, ring C, R, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 1 , wherein:{'sup': '1A', 'Ris selected from the group consisting of H and fluorine;'}{'sup': '1B', 'Ris selected from the group consisting of H and fluorine; and'}{'sup': '2', 'sub': '2', 'Ris selected from the group consisting of methyl and —CHF.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:ring C is selected from the group consisting of pyrazine and pyrimidine;p is 0 or 1; and{'sup': 'C', 'sub': 3', '2', '2', '2', '3, 'R(when present) is independently selected from the group consisting of methyl, ethyl, —CF, —CHF, —CHF, —CHOCH, and cyclopropyl.'}4. A compound of claim 3 , or a tautomer thereof claim 3 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 3 , wherein:ring A is selected from the group consisting of phenyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, triazinyl, thiazolyl, and thienyl;m is 0, 1, 2, or 3, with the proviso that the value of m does not exceed the number of available substitutable hydrogen atoms on ring A; and{'sup': 'A', 'sub': 3', '2', '3', '3', ...

NOVEL SPIRO IMIDAZOLONE DERIVATIVES AS GLUCAGON RECEPTOR ANTAGONISTS, COMPOSITIONS, AND METHODS FOR THEIR USE

The present invention relates to compounds of the general formula (I): wherein ring A, ring B, G, R, Z, L, and Lare selected independently of each other and are as defined herein, to compositions comprising the compounds, and to methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto. 17. A composition comprising a compound according to and a pharmaceutically acceptable carrier.18. A composition of claim 17 , further comprising one or more other antidiabetic agents.19. (canceled)20. A composition of claim 17 , further comprising at least one additional therapeutic agent selected from the group consisting of: DPP-IV inhibitor claim 17 , an insulin sensitizer claim 17 , insulin claim 17 , an insulin mimetic claim 17 , an insulin secretagogue claim 17 , a GLP-1 mimetic claim 17 , a glucosidase inhibitor claim 17 , an alpha glucosidase inhibitor claim 17 , a glucagon receptor antagonist other than a compound of claim 17 , glucophage claim 17 , glucophage XR claim 17 , an antihypertensive agent claim 17 , a meglitinide claim 17 , an alpha-glucosidase inhibitor claim 17 , amlintide claim 17 , pramlintide claim 17 , exendin claim 17 , a histamine Hreceptor antagonist claim 17 , dapagliflozin claim 17 , sergliflozin claim 17 , AVE2268 (Sanofi-Aventis) and T-1095 (Tanabe Seiyaku) claim 17 , a cholesterol lowering agent claim 17 , a PACAP claim 17 , a PACAP mimetic claim 17 , a PACAP receptor 3 agonist claim 17 , a PPAR delta agonist claim 17 , an antiobesity agent claim 17 , an ileal bile acid transporter inhibitor claim 17 , an NSAID claim 17 , and a CB1 receptor antagonist claim 17 , and a CB1 receptor inverse agonist.21. A method for treating type 2 diabetes mellitus in a patient in need thereof claim 1 , comprising administering to said patient at least one compound according to in an amount that is effective to treat type 2 diabetes mellitus.2231-. (canceled) The present ...

Substituted piperazines as CB1 antagonists

Compounds of Formula (I): or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Substituted aminoquinazoline compounds as A2A antagonist

The present invention is directed to compounds of generic formula (I): or pharmaceutically acceptable salts thereof that are believed to be useful as an A2A-receptor antagonist. The invention is further directed to methods of treating a patient (preferably a human) for diseases or disorders in which the A2A-receptor is involved. The invention further involves use of the compounds as an A2A-receptor antagonist and/or inhibitor for the preparation of a medicament for the treatment and/or prevention of diseases associated with inhibiting the receptor, which includes central nervous system disorders such as Parkinson's disease. The invention is also directed to pharmaceutical compositions which include an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, X, U, R1, R2, R3, and R4, are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist.

C6-AZASPIRO IMINOTHIADIAZINE DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain C2-ring-substituted thiadiazine compounds, including compounds Formula (I): (structure represented) or tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R, R, ring A, R, m, -L-, R, and ring C are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed. 3. A compound of claim 2 , or a tautomer thereof claim 2 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 2 , wherein:ring A is selected from the group consisting of phenyl, pyridazinyl, pyridyl, pyrimidinyl, pyrazinyl, triazinyl, and tetrazinyl;m is 0, 1, or 2; and{'sup': 'A', 'sub': 5', '3', '3', '2', '3', '2', '3', '2', '2', '3', '3', '2', '3', '2', '2', '3', '2, 'each R(when present) is independently selected from the group consisting of halogen, oxo, —CN, —SF, —NHCH, —N(CH), —OCH, —OCHCH, —O-cyclopropyl, —O—CH-cyclopropyl, —CHOCH, —S(CH), methyl, ethyl, cyclopropyl, —CH-cyclopropyl, —CF, —CHF, —CHF, —OCF, and —OCHF.'}4. A compound of claim 3 , or a tautomer thereof claim 3 , or a pharmaceutically acceptable salt of said compound or said tautomer claim 3 , wherein:{'sup': 'L', 'sub': 3', '2', '2', '2', '3', '2', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2', '3', '2', '2, 'Ris selected from the group consisting of methyl, ethyl, propyl, butyl, —CF, —CHF, —CHF, —CHCF, —CFCH, —CHOCH, —CHOCHCH, —CHCHOCH, —CHSCH, —CHSCHCH, —CHCHSCH, —CHN(CH), —CHNHCH, —CHCHN(CH), —CHOCF, and —CHOCHF.'}9. A pharmaceutical composition comprising a ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, U, X, R1, R2, R3, and R4 are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist ...

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Xanthine phosphodiesterase V inhibitors

A xanthine phosphodiesterase V inhibitor having the formula (I), with the variables defined herein, which is especially useful for treating male (erectile) and female sexual dysfunction and other physiological disorders: For example, a representative compound of the invention is:

SUBSTITUTED CYCLOPROPLY COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included 2. The compound of claim 1 , wherein ring A is phenyl claim 1 , pyridinyl claim 1 , pyrimidinyl claim 1 , pyridazinyl claim 1 , or pyrazinyl.3. The compound of claim 1 , wherein ring A is phenyl or pyrimidine.4. The compound of claim 1 , wherein ring A is a pyridine ring.8. The compound of claim 1 , wherein B is C(O)R claim 1 , or C(O)OR.10. The compound of claim 1 , wherein Rrepresents a member selected from the group consisting of 3- to 6-membered heterocyclyl claim 1 , containing 1-3 O claim 1 , S claim 1 , or N claim 1 , optionally substituted by oxo; 5-membered heteroaryl claim 1 , containing 1-4 O claim 1 , S claim 1 , or N claim 1 , optionally substituted by Calkyl; aryl; C(O)Calkyl; C(O)Ccycloalkyl; SOCalkyl; SOCcycloalkyl; CN; C(O)NRR; and CHC(O)NRR.11. The compound of claim 10 , wherein R′ is 5-membered heteroaryl claim 10 , containing 1-4 O claim 10 , S claim 10 , or N claim 10 , optionally substituted by Calkyl.12. The compound of claim 11 , wherein Ris SOCalkyl claim 11 , or SOCcycloalkyl.13. The compound of claim 12 , wherein Ris C(O)NRRor CHC(O)NRR.14. The compound of claim 1 , wherein each Ris methyl claim 1 , chloro claim 1 , fluoro claim 1 , CN claim 1 , or methoxy.17. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and a pharmaceutically acceptable carrier.1821-. (canceled)22. A method for the treatment of a condition selected from the group consisting of obesity and diabetes comprising administering to an individual a pharmaceutical composition comprising the compound of . The present invention relates to G-protein coupled receptor agonists. ...

5-SUBSTITUTED IMINOTHIAZINES AND THEIR MONO- AND DIOXIDES AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , said tautomer claim 1 , or said stereoisomer claim 1 , wherein:{'sub': '2', 'W is S(O).'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a stereoisomer of said compound or said tautomer claim 2 , or a pharmaceutically acceptable salt of said compound claim 2 , said tautomer claim 2 , or said stereoisomer claim 2 , wherein:{'sup': '4', 'Ris selected from the group consisting of lower alkyl and lower haloalkyl.'}4. A compound of claim 3 , or a tautomer thereof claim 3 , or a stereoisomer of said compound or said tautomer claim 3 , or a pharmaceutically acceptable salt of said compound claim 3 , said tautomer claim 3 , or said stereoisomer claim 3 , wherein:{'sup': 9', '10, 'one of Rand Ris H and the other is selected from the group consisting of H, lower alkyl, lower haloalkyl, and lower alkyl ether.'}5. A compound of claim 3 , or a tautomer thereof claim 3 , or a stereoisomer of said compound or said tautomer claim 3 , or a pharmaceutically acceptable salt of said compound claim 3 , said tautomer claim 3 , or said stereoisomer claim 3 , wherein:{'sup': '1A', 'Ris selected from ...

6,7-dihydro-5h-pyrrolo[3,4-b]pyridin-5-one allosteric modulators of the m4 muscarinic acetylcholine receptor

The present invention is directed to 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

SUBSTITUTED CYCLOPROPYL COMPOUNDS, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF TREATMENT

Substituted cyclopropyl compounds of the formula I and the pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the g-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included. Another aspect of the invention that is of interest relates to compounds of formula Ia.

6,7-DIHYDRO-5H-PYRROLO[3,4-B]PYRIDIN-5-ONE ALLOSTERIC MODULATORS OF THE M4 MUSCARINIC ACETYLCHOLINE RECEPTOR

The present invention is directed to 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved. 2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris selected from the group consisting of: benzodioxolyl claim 1 , benzoimidazolyl claim 1 , benzoxazoly claim 1 , benzooxazinone claim 1 , benzooxazolone claim 1 , benzothiazolyl claim 1 , chromanyl claim 1 , cyclopentapyridinyl claim 1 , dihydrobenzo[1 claim 1 ,4]dioxinyl claim 1 , dihydrobenzofuranyl claim 1 , dihydrobenzo[1 claim 1 ,4]oxazinyl claim 1 , dihydrofuropyridinyl claim 1 , dihydroisobenzofuranyl claim 1 , dihydroisoquinolinone claim 1 , dihydropyranopyridinyl claim 1 , dihydroimidazopyridine claim 1 , dihydropyrido[1 claim 1 ,4]oxazinyl claim 1 , dihydroquinolinone claim 1 , indazolyl claim 1 , indanyl claim 1 , indolyl claim 1 , isochromanone claim 1 , isobenzofuranone claim 1 , isochromanyl claim 1 , isoindolinyl claim 1 , isoxazolyl claim 1 , oxoisoindolinyl claim 1 , phenyl claim 1 , pyrazolopyridinyl claim 1 , pyrazolyl claim 1 , pyridyl claim 1 , pyrrolopyridinyl claim 1 , pyrimidinyl claim 1 , quinolinone claim 1 , quinolinyl claim 1 , tetrahydrofuranyl claim 1 , tetrahydroisoquinolinyl claim 1 , tetrahydroquinolinyl claim 1 , and tetrahydropyranyl claim 1 , which is substituted with R claim 1 , Rand R.3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , ...

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): 119-. (canceled)23. The pharmaceutical composition of claim 22 , wherein said pharmaceutically acceptable salt is selected from the group consisting of acetate claim 22 , ascorbate claim 22 , benzoate claim 22 , benzenesulfonate claim 22 , bisulfate claim 22 , borate claim 22 , butyrate claim 22 , citrate claim 22 , camphorate claim 22 , camphorsulfonate claim 22 , fumarate claim 22 , hydrochloride claim 22 , hydrobromide claim 22 , hydroiodide claim 22 , lactate claim 22 , maleate claim 22 , methanesulfonate claim 22 , naphthalenesulfonate claim 22 , nitrate claim 22 , oxalate claim 22 , phosphate claim 22 , propionate claim 22 , salicylate claim 22 , succinate claim 22 , sulfate claim 22 , tartarate claim 22 , thiocyanate claim 22 , and toluenesulfonate.24. The pharmaceutical composition of claim 22 , wherein said pharmaceutically acceptable salt is a hydrochloride salt.25. The pharmaceutical composition of claim 22 , wherein said pharmaceutically acceptable salt is a toluenesulfonate salt.28. The pharmaceutical composition of claim 27 , wherein said pharmaceutically acceptable salt is selected from the group consisting of acetate claim 27 , ascorbate claim 27 , benzoate claim 27 , benzenesulfonate claim 27 , bisulfate claim 27 , borate claim 27 , butyrate claim 27 , citrate claim 27 , camphorate claim 27 , camphorsulfonate claim 27 , fumarate claim 27 , hydrochloride claim 27 , hydrobromide claim 27 , hydroiodide claim 27 , lactate claim 27 , maleate claim 27 , methanesulfonate claim 27 , naphthalenesulfonate claim 27 , nitrate claim 27 , oxalate claim 27 , phosphate claim 27 , propionate claim 27 , salicylate claim 27 , succinate claim 27 , sulfate claim 27 , tartarate claim 27 , thiocyanate claim 27 , and toluenesulfonate.29. The pharmaceutical composition of claim 27 , wherein said pharmaceutically acceptable salt is a ...

IMINOTHIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): 119-. (canceled)21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the compound of or a tautomer thereof.23. The pharmaceutically acceptable salt of claim 22 , wherein said salt is selected from the group consisting of acetate claim 22 , ascorbate claim 22 , benzoate claim 22 , benzenesulfonate claim 22 , bisulfate claim 22 , borate claim 22 , butyrate claim 22 , citrate claim 22 , camphorate claim 22 , camphorsulfonate claim 22 , fumarate claim 22 , hydrochloride claim 22 , hydrobromide claim 22 , hydroiodide claim 22 , lactate claim 22 , maleate claim 22 , methanesulfonate claim 22 , naphthalenesulfonate claim 22 , nitrate claim 22 , oxalate claim 22 , phosphate claim 22 , propionate claim 22 , salicylate claim 22 , succinate claim 22 , sulfate claim 22 , tartarate claim 22 , thiocyanate claim 22 , and toluenesulfonate.24. The pharmaceutically acceptable salt of claim 22 , wherein said salt is a hydrochloride salt.25. The pharmaceutically acceptable salt of claim 22 , wherein said salt is a toluenesulfonate salt.26. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a pharmaceutically acceptable salt of .27. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the pharmaceutically acceptable salt of .28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the pharmaceutically acceptable salt of .30. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and the compound of or a tautomer thereof.32. The pharmaceutically acceptable salt of the compound or tautomer of claim 31 , wherein said salt is selected from the group consisting of acetate claim 31 , ascorbate claim 31 , benzoate claim 31 , benzenesulfonate claim 31 , bisulfate ...

TRICYCLIC SUBSTITUTED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS AND THEIR USE

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 5-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , said tautomer claim 1 , or said stereoisomer claim 1 , wherein:{'sup': '4', 'sub': 3', '2, 'Ris selected from the group consisting of —CHand —CHF; and'}{'sup': 9', '10, 'one of Rand Ris H and the other is selected from the group consisting of H, halo, lower alkyl, cycloalkyl, lower haloalkyl, and lower heteroalkyl.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a stereoisomer of said compound or said tautomer claim 2 , or a pharmaceutically acceptable salt of said compound claim 2 , said tautomer claim 2 , or said stereoisomer claim 2 , wherein:ring B is selected from the group consisting of pyrrolyl, imidazolyl, oxadiazolyl, triazolyl, isoxazolyl, oxazolyl, thienyl, pyrazolyl, furanyl, tetrazolyl, thiazolyl, and isothiazolyl.4. A compound of claim 3 , or a tautomer thereof claim 3 , or a stereoisomer of said compound or said tautomer claim 3 , or a pharmaceutically acceptable salt of said compound claim 3 , said tautomer claim 3 , ...

TRICYCLIC SUBSTITUTED THIADIAZINE DIOXIDE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS AND THEIR USE

In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoisomers, wherein the middle ring (referred to herein as “ring B”) of the tricyclic substituent is an optionally substituted 6-membered ring, and each of the remaining variables shown in the formula are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed. 2. A compound of claim 1 , or a tautomer thereof claim 1 , or a stereoisomer of said compound or said tautomer claim 1 , or a pharmaceutically acceptable salt of said compound claim 1 , said tautomer claim 1 , or said stereoisomer claim 1 , wherein:{'sup': '4', 'sub': 3', '2, 'Ris selected from the group consisting of —CHand —CHF; and'}{'sup': 9', '10, 'one of Rand Ris H and the other is selected from the group consisting of H, halo, lower alkyl, cycloalkyl, lower haloalkyl, and lower heteroalkyl.'}3. A compound of claim 2 , or a tautomer thereof claim 2 , or a stereoisomer of said compound or said tautomer claim 2 , or a pharmaceutically acceptable salt of said compound claim 2 , said tautomer claim 2 , or said stereoisomer claim 2 , wherein:ring B is selected from the group consisting of phenyl, pyridyl, tetrahydropyridyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, piperdinyl, and piperazinyl.4. A compound of claim 3 , or a tautomer thereof claim 3 , or a stereoisomer of said compound or said tautomer claim 3 , or a pharmaceutically acceptable salt of said compound claim 3 , said tautomer claim 3 , or said stereoisomer ...

Bicyclic heterocycle derivatives and their use as gpcr modulators

The present invention relates to Bicyclic Heterocycle Derivatives of Formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a diabetic complication, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G protein-coupled receptor (GPCR) in a patient.

Bicyclic heterocycle derivatives and their use as modulators of the activity of gpr119

The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

Pyrimidinone derivatives and methods of use thereof

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disease, a cardiovascular disease or a disorder related to the activity of GPR119 in a patient.

Pyrimidinone derivatives and methods of use thereof

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of G protein-coupled receptor 119 ('GPR119') in a patient.

Azetidinone derivatives and methods of use thereof

The present invention relates to methods for treating or preventing a disorder of lipid metabolism, pain, diabetes, a vascular condition, demyelination or nonalcoholic fatty liver disease, comprising administering a compound having the formula (I) or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof, wherein: R1 and R2 are defined in Tables 1-6 herein, and R3 is -phenyl, -4-chlorophenyl, -2-pyridyl, or -3-pyridyl.

Treating pain, diabetes, and lipid metabolism disorders

Disclosed is a method of treating a disease or condition (e.g., pain, diabetes or disorders of lipid metabolism) comprising administering an azetidine derivative of the formula (I) selected from the group consisting of the compounds defined by Tables 1, 2, 3a, 3b, 3c, 3d and 4a.

Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R 1 , R 2 , R 3 , R 4 , R 5 , R 9 , ring A, ring B, m, n, p, -L 1 -,L 2 -, and L 3 - is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

5-substituted iminothiazines and their mono-and dioxides as bace inhibitors,compositions,and their use

The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoismers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed.

Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of W, Z, R 1H , R 2 , R 3 , R 4 , ring A, ring B, m, n, p, and- L 1 - is as defined herein. The novel compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use

Diazine-fused amidine compounds as bace inhibitors, compositions, and their use

New neuropeptide y y5 receptor antagonists

The present invention discloses compounds which, are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

New neuropeptide y y5 receptor antagonists

The present invention discloses compounds which, are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

Fused tricyclic heterocyclic compounds as hiv integrase inhibitors

The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.

Aspartyl protease inhibitors.

Se revelan compuestos de formula I (ver formula I) o su estereoisomero, tautomero o sal aceptable para uso farmaceutico, donde U, W, R, R1, R2, R3 y R4 son segun se definieron en la memoria descriptiva; y composiciones farmaceuticas que comprenden los compuestos de formula I; Tambien se revela el metodo para inhibir aspartil proteasas y, en particular, los metodos para tratar enfermedades cardiovasculares, enfermedades cognitivas y neurodegenerativas. Tambien se revelan metodos para tratar enfermedades cognitivas o neurodegenerativas utilizando los compuestos de formula I en combinacion con un inhibidor de colinesterasa o un agonista m1 o antagonista m2 muscarinico.

2-heteroaryl-pyrazolo-[4, 3-e]-1, 2, 4-triazolo-[1,5-c]-pyrimidine as adenosine a2a receptor antagonists

Compounds having the structural formula (I) or a pharmaceutically acceptable salt thereof, wherein R is R1-isoxazolyl, R1-oxadiazolyl, R1-dihydrofuranyl, R1-pyrazolyl, R1-imidazolyl, R1-pyrazinyl or R1-pyrimidinyl; R1 is 1 , 2 or 3 substituents selected from H, alkyl, alkoxy and halo; Z is optionally substituted-aryl, or optionally substituted-heteroaryl; are disclosed, as well as their use in the treatment of central nervous system diseases, in particular Parkinson's disease and Extra Pyramidal Syndrome, pharmaceutical compositions comprising them, and combinations with other agents.

Xanthine phosphodiesterase v inhibitors

Treating pain, diabetes, and disorders of lipid metabolism.

Se describe un método para tratar una enfermedad o afección (por ejemplo, dolor, diabetes o trastornos del metabolismo de los lípidos) que comprende administrar un derivado de azetidina de fórmula I (ver fórmula (I)) seleccionado del grupo que consiste en los compuestos definidos por los cuadros 1, 2, 3a, 3b, 3c, 3d, y 4a.

5-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions, and their use

The present invention discloses certain iminothiazine compounds and mono- and dioxides thereof, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomers and said stereoismers, wherein each of variables shown in the formula are as defined herein. The compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and uses, including Alzheimer's disease, are also disclosed.

Substituted cyclopropyl compounds, compositions containing such compounds as well as their use in treating type-2 diabetes

Substituted piperazines as cb1 antagonists

Compounds of Formula (I): (see formula I) or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.

Substituted piperazines as CB1 antagonists

Un compuesto de Fórmula (I): o una sal, solvato o éster farmacéuticamente aceptables de los mismos, en la que: Ar1 y Ar2 son independientemente fenilo o piridilo, en la que dichos fenilo y piridilo están sustituidos con uno o más grupos Y1; n y m son independientemente 0 o 1; A se selecciona del grupo que consiste en -C(O)-, -S(O)2-, -C(>=N-OR2)- y -(C(R2)2)q-, en el que q es 1, 2 o 3; B se selecciona del grupo que consiste en -N(R2)-, -C(O)- y -(C(R3)2)r-, en el que r es 1 o 2, con la condición de que cuando B sea -C(O)-, entonces A es -C(O)- o -(C(R2)2)q-; X se selecciona del grupo que consiste en H, alquilo, -S-alquilo, -S(O)2-alquilo, -S(O)2-cicloalquilo, -S(O)2-arilo, - S(O)2-heteroarilo, cicloalquilo, cicloalquilo benzo-condensado, heterocicloalquilo benzo-condensado, heterocicloalquenilo benzo-condensado, heterocicloalquilo, -C(R2)>=C(R2)-arilo, -C(R2)>=C(R2)-heteroarilo, -OR2, -Oalquileno-O-alquilo, -S-arilo, -N(R4)2, -(C(R2)2)s-heteroarilo, -C(O)-O-alquilo, -C(O)-arilo, -C(O)-heteroarilo, -N>=O, - C(S-alquil)>=N-S(O)2-arilo, -C(N(R2)2)>=N-S(O)2-arilo y -(C(R2)2)s-arilo, en los que s es 0, 1 o 2. A compound of Formula (I): or a pharmaceutically acceptable salt, solvate or ester thereof, wherein: Ar1 and Ar2 are independently phenyl or pyridyl, wherein said phenyl and pyridyl are substituted with one or more Y1 groups; n and m are independently 0 or 1; A is selected from the group consisting of -C (O) -, -S (O) 2-, -C (> = N-OR2) - and - (C (R2) 2) q-, where q is 1, 2 or 3; B is selected from the group consisting of -N (R2) -, -C (O) - and - (C (R3) 2) r-, where r is 1 or 2, with the proviso that when B is -C (O) -, then A is -C (O) - or - (C (R2) 2) q-; X is selected from the group consisting of H, alkyl, -S-alkyl, -S (O) 2-alkyl, -S (O) 2-cycloalkyl, -S (O) 2-aryl, - S (O) 2 -heteroaryl, cycloalkyl, benzo-condensed cycloalkyl, benzo-condensed heterocycloalkyl, benzo-condensed heterocycloalkenyl, heterocycloalkyl, -C (R2)> = C (R2) - ...

1,2,4-triazolo[4,3-c]pyrimidin-3-one and pyrazolo [4,3-e] -1,2,4-triazolo [4,3-c] pyrimidin-3-one compounds for use as adenosine a2a receptor antagonists

Compounds of the Formula I wherein R 1 and R 2 together with the carbon atoms to which they are bonded optionally form a further heteroaromatic ring of the formula (II) as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-,L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to ß-amyloid (Aß) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aß) protein, including Alzheimers disease, are also disclosed.

Aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein (W, R1, R2, R3, R4, R5, R6, and R7) are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin (D) and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Diazine-fused amidine compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R 1A , R 1B , R 2 , R A , ring A, R A , m, L 1 , R L , ring C, R C , and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula(a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

Xanthine phosphodiesterase V inhibitors

Diazine-fused amidine compounds as bace inhibitors, compositions, and their use

In its many embodiments, the present invention provides certain C-6 spirocarbocyclic iminothiadiazine compounds, including compounds Formula (I) or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R 1A , R 1B , R 2 , R A , ring A, R A , m, L 1 , R L , ring C, R C , and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Heterocyclic aspartyl protease inhibitors

Det er beskrevet forbindelser med formel (I) en stereoisomer, tautomer eller et farmasøytisk akseptabelt salt eller solvat derav, hvor W er en binding, -C(=S)-, -S(O)-, -S(O)2-, -C(=O)-, -O-, -C(R6)(R7), -N(R5)- eller -C(=N(R5))-; X er -O-, -N(R5)- eller -C(R6)(R7)-; forutsatt at når X er -O-, er U ikke -O-, -S(O)-, -S(O)2-, -C(=O)- eller -C(=NR5)-; U er en binding, -S(O)-, -S(O)2-, -C(O)-, -O-, -P(O)(OR15)-, -C(=NR5)-, -(C(R6)(R7))b- eller -N(R5)-, hvor b er 1 eller 2; forutsatt at når W er -S(O)-, -S(O)2-, -O- eller -N(R5)-, er U ikke -S(O)-, -S(O)2-, -O- eller -N(R5)-; forutsatt at når X er -N(R5) og W er -S(O)-, -S(O)2-, -O- eller -N(R5)-, er U ikke en binding; og R1, R2, R3, R4, R5, R6 og R7 er som definert i beskrivelsen; og farmasøytiske preparater som omfatter forbindelsene med formel (I). Det er også beskrevet en fremgangsmåte for hemming av aspartylprotease, og særlig fremgangsmåtene for behandling av kardiovaskulære sykdommer, kognitive og neurodegenerative sykdommer, og fremgangsmåtene for hemming av humant immunsviktvirus, plasmepiner, kathepsin D og protozoenzymer. Det er også beskrevet fremgangsmåter for behandling av kognitive eller neurodegenerative sykdommer under anvendelse av forbindelsene med formel I i kombinasjon med en kolinesteraseinhibitor eller en muskarin m1-agonist eller m2-antagonist.

Macrocyclic β-secretase inhibitors

Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 , R 2 , R 3 , n and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

Treating pain, diabetes and lipid metabolism disorders

Disclosed is a method of treating a disease or condition (e.g., pain, diabetes or disorders of lipid metabolism) comprising administering an azetidine derivative of the formula (I) selected from the group consisting of the compounds defined by Tables 1, 2, 3a, 3b, 3c, 3d and 4a.

Treating pain, diabetes, and lipid metabolism disorders

Disclosed is a method of treating a disease or condition (e.g., pain, diabetes or disorders of lipid metabolism) comprising administering an azetidine derivative of the formula (I) selected from the group consisting of the compounds defined by Tables 1, 2, 3a, 3b, 3c, 3d and 4a.

Heterocyclic aspartyl protease inhibitors

Disclosed are compounds of the formula I Chemical formula should be inserted here as it appears on the abstract in paper form. or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment

Aspartyl protease inhibitors

Disclosed are compounds of the formula (I) Chemical formula should be inserted here as it appears on the abstract in paper form or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein U, W, R, R1, R2, R3 and R4 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

Pyrimidinone derivatives and methods of use thereof

The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of G protein-coupled receptor 119 ('GPR119') in a patient.

Substituted aminoquinazoline compounds as a2a antagonist

Substituted piperazines as cb1 antagonists

Compounds of Formula (I) or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardio-vascular conditions.

Bicyclic heterocycle derivatives and their use as modulators of the activity of gpr119

SUBSTITUTED IMIDAZOLE AS NEUROPEPTIDE Y Y5 RECEPTOR ANTAGONISTS

Inhibitors of ENL/AF9 YEATS

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula inhibit ENL/AF

Neuropeptide y5 receptor antagonists

Compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein a and b are 0-2, provided that the sum is 0-3; Q is (i) or (-N=); X is -O-, -S-, -SO-, -SO2-, -CH(OR8)-, -C(O)-, -C(R23)2-, optionally substituted alkenyl, alkynyl or (ii); R1 is optionally substituted aryl, heteroaryl, substituted amino, alkyl-OC(O)R8, aryloxyalkyl, (iii) wherein m is 1-4, or (iv) wherein d and e are 0-2; R2, R3, R4 and R5 are H, alkyl, optionally substituted cycloalkyl, halogen, -OR8, -N(R8)2, -CO2R8 or CF3; R6 and R7 are H, alkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, cycloalkyl or cycloalkylalkyl, or R6 and R7, form a 3-7-membered carbocyclic ring, or a 4-7-membered heterocyclic ring; R8 is H, alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R9 is alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R11 is H, alkyl or cycloalkyl; and R23 is R8 or halogen; are claimed, as well as additional novel compounds; also claimed are pharmaceutical compositions and methods of using said novel compounds in the treatment of eating disorders and diabetes.

Inhibitors of enl/af9 yeats

Methods and compositions for treating leukemia are disclosed. Acylated 6-aminoindoles, acylated 6-aminopyrrolopyridines and acylated 3-aminopyrrolo[3,2-c]pyridazines of the following formula inhibit ENL/AF9 YEATS and are therefore useful for treating leukemia.

C2-azaspiro iminothiazine dioxides as bace inhibitors

In its many embodiments, the present invention provides certain C2-azaspirosubstituted iminothiazine dioxide compounds. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use

Heteroaryl urea neuropeptide y y5 receptor antagonists

The present invention relates to compounds represented by the structural Formula I or a pharmaceutically acceptable salt thereof, which are useful for the treatment of metabolic and eating disorders such as obesity and hyperphagia, and for the treatment of diabetes and associated disorders.

Neuropeptide y5 receptor antagonists

Compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein a and b are 0-2, provided that the sum is 0-3; Q is (i) or (-N=); X is -O-, -S-, -SO-, -SO2-, -CH(OR8)-, -C(O)-, -C(R23)2-, optionally substituted alkenyl, alkynyl or (ii); R1 is optionally substituted aryl, heteroaryl, substituted amino, alkyl-OC(O)R8, aryloxyalkyl, (iii) wherein m is 1-4, or (iv) wherein d and e are 0-2; R?2, R3, R4 and R5¿ are H, alkyl, optionally substituted cycloalkyl, halogen, -OR?8, -N(R8)¿2, -CO2R8 or CF¿3?; R?6 and R7¿ are H, alkyl, alkenyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, cycloalkyl or cycloalkylalkyl, or R?6 and R7¿, form a 3-7-membered carbocyclic ring, or a 4-7-membered heterocyclic ring; R8 is H, alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R9 is alkyl, cycloalkyl, optionally substituted aryl or heteroaryl; R11 is H, alkyl or cycloalkyl; and R?23 is R8¿ or halogen; are claimed, as well as additional novel compounds; also claimed are pharmaceutical compositions and methods of using said novel compounds in the treatment of eating disorders and diabetes.

SUBSTITUTED AMIDS AS INHIBITORS OF BETA-SEKRETASE

Substituted imidazole neuropeptide y y5 receptor antagonists

Compounds of formula (I) or a pharmaceutically acceptable salt, solvate or N-oxide thereof, wherein X is =CH- or =N-; Y is H, halogen, trihaloalkyl, alkyl, alkenyl, cycloalkyl, cycloalkyl, SH, -S-alkyl, or -CN. R is alkyl, -CF3, cycloalkyl, heterocycloalkyl, heterocycloalkyl-alkyl, heteroarylalky or adamantyl, or optionally substituted phenyl, phenoxyalkyl, phenylthioalkyl, pyridyl, thienyl, thiazolyl, pyrazinyl, 1,2,5 ,6- tetrahydropyridine or formula (A), wherein R10 and R11 are hydrogen, alkyl or together form a cycloalkyl, are disclosed, as wel l as pharmaceutical compositions and methods of using said compounds in the treatment of eating disorders and diabetes.

Xanthines, inhibitors of type V phosphodiesterase

Μια ξανθίνη αναστολέας φωσφοδιεστεράσης V που έχει τον τύπο (I), όπου R4 είναι μια C3-15 κυκλοαλκυλ ομάδα, με ή χωρίς ένα ή περισσότερα υποκατάστατα, C3-15 κυκλοαλκυλ ομάδα, με ή χωρίς ένα ή περισσότερα υποκατάστατα, ή μια ετεροκυκλοαλκυλ ομάδα που έχει 3 έως 15 μέλη, με ή χωρίς ένα ή περισσότερα υποκατάστατα, η οποία είναι χρήσιμη για θεραπεία ανδρικής(στυτικής) και γυναικείας δυσλειτουργίας και άλλων φυσιολογικών διαταραχών. Για παράδειγμα, μια αντιπροσωπευτική ένωση του εφευρετικού τύπου (II). A phosphodiesterase V xanthine inhibitor of formula (I), wherein R 4 is a C 3-15 cycloalkyl group, with or without one or more substituents, a C 3-15 cycloalkyl group, with or without one or more substituents, or a heterocycloalkyl group has 3 to 15 members, with or without one or more substitutes, which is useful for the treatment of male (erectile) and female dysfunction and other physiological disorders. For example, a representative compound of the inventive formula (II).

Aspartyl protease inhibitors

Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein (W, R1, R2, R3, R4, R5, R6, and R7) are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin (D) and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Xanthine phosphodiesterase v inhibitors

A xanthine phosphodiesterase V inhibitor having the formula (I), where R4 is a C¿3-15? cycloalkyl group, with or without one or more substituents, C3-15 cycloalkenyl group, with or without one or more substituents, or a heterocycloalkyl group of 3 to 15 members, with or without one or more substituents; useful for treating male (erectile) and female sexual dysfunction and other physiological disorders. For example, a representative compound of the invention is formula (II).