PYRROLIDINE GPR40 MODULATORS

The present invention provides compounds of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a polymorph, or a solvate thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments. 4. A compound of Formula (I) or (II) according to claim 3 , or a stereoisomer claim 3 , a tautomer claim 3 , a pharmaceutically acceptable salt claim 3 , or a solvate thereof claim 3 , wherein:{'sup': 1', '6', '6, 'Ris independently phenyl substituted with 0-3 Ror a heteroaryl substituted with 0-2 R; wherein said heteroaryl is selected from: thiazolyl, pyridinyl, pyrimidinyl, and pyrazinyl.'}5. A compound of Formula (I) according to claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , a pharmaceutically acceptable salt claim 1 , or a solvate thereof claim 1 , wherein:{'sup': 1', '6', '6', '6', '6', '6, 'R, at each occurrence, is independently phenyl substituted with 0-3 R, pyridinyl substituted with 0-2 R, pyrazinyl substituted with 0-2 R, pyrimidinyl substituted with 0-2 R, or thiazolyl substituted with 0-2 R;'}{'sup': '2', 'sub': 1-6', '1-6, 'R, at each occurrence, is independently selected from: OH, halogen, Calkyl substituted with 0-1 CN, Calkoxy, benzyl, and tetrazolylmethyl;'}{'sup': '6', 'sub': 1-8', '1-4', '1-4', '1-4', '3-6', '1-4', '5-6', '1-4', '3-6, 'R, at each occurrence, is independently selected from: halogen, CN, Calkyl, Calkoxy, Chaloalkyl, Chaloalkoxy, Ccycloalkyl substituted with 0-2 Calkyl, Ccycloalkenyl substituted with 0-2 Calkyl, —O—Ccycloalkyl, benzyl, and oxazolyl; and'}{'sup': '10', 'sub': 1-4', '1-4', '1-4', '1-4', '2', '1-2, 'R, at each occurrence, is independently selected from: halogen, CN, Calkyl, Calkoxy, Chaloalkyl, Chaloalkoxy, and CO(Calkyl).'}6. A compound of Formula (I) according to claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , a pharmaceutically acceptable salt claim 1 , or a solvate thereof claim 1 , ...

PYRROLIDINE GPR40 MODULATORS

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments. 9. A compound according to claim 7 , wherein:{'sup': 1', '6', '6, 'Ris independently phenyl substituted with 0-3 Ror pyridinyl substituted with 0-2 R;'}{'sup': '2', 'sub': '1-4', 'Ris independently halogen or Calkyl;'}{'sup': '3', 'sub': 1-4', '1-4', '3, 'Ris independently selected from: halogen, Calkyl, Calkoxy, CF, phenyl, benzyl, and phenoxy;'}{'sup': '4a', 'sub': '1-4', 'Ris independently selected from: H, halogen and Calkyl; and'}{'sup': '6', 'sub': 1-4', '1-4, 'R, at each occurrence, is independently selected from: halogen, Calkyl, and Calkoxy.'}10. A compound according to claim 1 , wherein the compound is selected from the exemplified examples or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.11. A pharmaceutical composition claim 1 , comprising a pharmaceutically acceptable carrier and a compound of claim 1 , or a stereoisomer claim 1 , a tautomer claim 1 , or a pharmaceutically acceptable salt thereof.12. The pharmaceutical composition according to claim 11 , further comprising one or more other suitable therapeutic agents useful in the treatment of the aforementioned disorders including: anti-diabetic agents claim 11 , anti-hyperglycemic agents claim 11 , anti-hyperinsulinemic agents claim 11 , anti-retinopathic agents claim 11 , anti-neuropathic agents claim 11 , anti-nephropathic agents claim 11 , anti-atherosclerotic agents claim 11 , anti-ischemic agents claim 11 , anti-hypertensive agents claim 11 , anti-obesity agents claim 11 , anti-dyslipidemic agents claim 11 , anti-hyperlipidemic agents claim 11 , anti-hypertriglyceridemic agents claim 11 , anti-hypercholesterolemic agents claim 11 , anti-restenotic agents claim 11 , anti-pancreatic ...

BICYCLIC HETEROARLY ANALOGUES AS GPR119 MODULATORS

Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, Rand Rare defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds. 12. A pharmaceutical composition comprised of a therapeutically effective amount of a compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer or salt thereof claim 1 , of claim 1 , and a pharmaceutically acceptable carrier.13. The pharmaceutical composition of claim 12 , further comprising a therapeutically effective amount of one or more other therapeutically active agents.14. A method of modulating the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need thereof a therapeutically effective amount of at least one compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer or salt thereof claim 1 , of claim 1 , and optionally an additional therapeutic agent.15. A method for preventing claim 1 , inhibiting claim 1 , or treating the progression or onset of diseases or disorders associated with the activity of the GPR119 G protein-coupled receptor comprising administering to a mammalian patient in need of prevention claim 1 , inhibition claim 1 , or treatment a therapeutically effective amount of at least one compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer or salt thereof claim 1 , of claim 1 , and optionally an additional therapeutic agent wherein:(a) the diseases or ...

BENZOFURANYL ANALOGUES AS GPR119 MODULATORS

Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, where-in A, L, m, n, o, p, R, R, R, Rand Rare defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds. 3. The compound claim 1 , enantiomer claim 1 , diastereomer claim 1 , tautomer claim 1 , or salt thereof claim 1 , of claim 1 , wherein:{'sub': 4', '1', '6', '2', '6', '2', '6', '3', '12', '1', '6', '1', '6', '2', '1', '6', '1s', '19', '18', '19', '1', '6', '1', '6', '1', '6', '2', '1', '6', '18', '19', '1', '6', '2', '1', '6', '6-10', '1', '6', '1', '6, 'Ris a 5- to 10-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S; or a 5- to 10-membered heterocyclo, which contains 1-4 heteroatoms selected from N, O, and S; wherein the heteroaryl, and heterocyclo are substituted with one or more substituents selected from the group consisting of: halo, —OH, (C-C)-alkyl, (C-C)-alkenyl, (C-C)-alkynyl, (C-C)-cycloalkyl, (C-C)-alkyloxy, cyano, nitro, —COOH, —CO(C-C)-alkyl, —CO(C-C)-alkyl, —CONRR, —NRR, —(C-C)-alkylCOOH, —(C-C)-alkylOH, —(C-C)-alkyl(NH)COOH, —(C-C)-alkylCONRR, —(C-C)-alkyl-CO(C-C)-alkyl, (C)aryl, a 5- to 10-membered heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S, a 5- to 10-membered heterocyclo, which contains 1-4 heteroatoms selected from N, O, and S; halo(C-C)alkyl, and halo(C-C)alkyloxy.'}11. A pharmaceutical composition comprised of a therapeutically effective amount of a compound claim 1 , enantiomer claim 1 , ...

3-substituted propionic acids as alpha v integrin inhibitors

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to α V -containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of α v -containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

INDAZOLE DERIVATIVES AS ALPHA V INTEGRIN ANTAGONISTS

The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions. 9. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein X is Calkylene; and Y is a covalent bond or O.10. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein said compound is selected from the group consisting of:3-(6-Methoxypyridin-3-yl)-3-(4-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-indazol-1-yl)propanoic acid;3-(6-Methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-1H-indazol-1-yl)propanoic acid;3-(6-Methoxypyridin-3-yl)-3-(4-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-1H-indazol-1-yl)propanoic acid;(S)-2-(((Benzyloxy)carbonyl)amino)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-2H-indazol-2-yl)propanoic acid;3-Phenyl-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy)-1H-indazol-1-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy)-2H-indazol-2-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(6-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-2H-indazol-2-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(6-((2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-2H-indazol-2-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(6-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-2H-indazol-2-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(6-(2-(2-methyl-5,6,7,8- ...

3-SUBSTITUTED PROPIONIC ACIDS AS ALPHA V INTEGRIN INHIBITORS

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to α-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions. 2. The compound of or a pharmaceutically acceptable salt thereof claim 1 , wherein A claim 1 , L claim 1 , E claim 1 , G claim 1 , and L form a ring moiety selected from pyrazole claim 1 , pyrrole claim 1 , thiazole claim 1 , furan claim 1 , thiophene claim 1 , imidazole claim 1 , oxazole claim 1 , isoxazole claim 1 , isothiazole claim 1 , triazole claim 1 , oxadiazole claim 1 , thiadiazole claim 1 , pyrrolidine claim 1 , tetrahydrofuran claim 1 , imidazolidine claim 1 , pyrazolidine claim 1 , oxazolidine claim 1 , isoxazolidine claim 1 , thiazolidine claim 1 , isothiazolidine claim 1 , and dioxolane claim 1 , and wherein the ring moiety is substituted with 0 claim 1 , 1 claim 1 , or 2 Ror R.10. The compound of or a pharmaceutically acceptable salt thereof claim 1 , selected from:(±)-3-(6-Methoxypyridin-3-yl)-3-(3-(4-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)butyl)-1H-pyrazol-1-yl)propanoic acid;(±)-3-(6-Methoxypyridin-3-yl)-3-(3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-pyrazol-1-yl)propanoic acid;(S)-3-(6-Methoxypyridin-3-yl)-3-(3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-pyrazol-1-yl)propanoic acid;(R)-3-(6-Methoxypyridin-3-yl)-3-(3-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-pyrazol-1-yl)propanoic acid;(±)-2-(((Benzyloxy)carbonyl)amino)-3-(1-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)-1H-pyrazol-4-yl)propanoic ...

INDAZOLE DERIVATIVES AS ALPHA V INTEGRIN ANTAGONISTS

The present invention provides compounds of Formula (Ia) or (Ib): 115-. (canceled)231. The compound of claim or a pharmaceutically acceptable salt thereof , wherein said compound is:3-(6-methoxypyridin-3-yl)-3-(5-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl) ethoxy)pyrazolo[4,3-b]pyridin-1-yl)propanoic acid (11); or3-(6-methoxypyridin-3-yl)-3-(5-(3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl)-1H-pyrazolo[4,3-b]pyridin-1-yl)propanoic acid (113).24. A pharmaceutical composition comprising a compound of claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , and a carrier.25. A method of treating a disease claim 16 , disorder claim 16 , or condition selected from pathological fibrosis claim 16 , transplant rejection claim 16 , cancer claim 16 , osteoporosis claim 16 , and inflammatory disorders comprising administering a therapeutically effective amount of a compound of claim 16 , or a pharmaceutically acceptable salt thereof claim 16 , to a patient in need thereof.26. The method of wherein the pathological fibrosis is pulmonary claim 16 , liver claim 16 , renal claim 16 , cardiac claim 16 , dermal claim 16 , ocular claim 16 , or pancreatic fibrosis.27. The method of wherein the disease claim 16 , disorder claim 16 , or condition is idiopathic pulmonary fibrosis (IPF) claim 16 , nonalcoholic steatohepatitis (NASH) claim 16 , chronic kidney disease claim 16 , diabetic kidney disease claim 16 , or systemic sclerosis. This application claims the priority of U.S. Provisional Application Ser. No. 62/418,842 filed Nov. 8, 2016 which is herein incorporated by reference.The present invention relates to substituted azole amides and amines as αV integrin antagonists, pharmaceutical compositions comprising such compounds and to their use in therapy, especially in the treatment or prophylaxis of diseases, disorders, and conditions for which an αV integrin antagonist is indicated in a human.Integrins belong to a large family of α/β heterodimeric transmembrane ...

Bicyclic heteroaryl compounds as gpr119 modulators

Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, R 2 and R 4 are defined herein, are provided which are GPR119 G protein- coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

Benzofuranyl analogues as gpr119 modulators

Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, L, m, n, o, p, R 2, R 3 , R 3 , R 4 and R 5 are defined herein, are provided which are GPR1 19 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

Cyclic 11-beta hydroxysteroid dehydrogenase type i inhibitors

Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors

Novel compounds are provided which are 11-beta-hydroxysteroid dehydrogenase type I inhibitors. 11-Beta-hydroxysteroid dehydrogenase type I inhibitors are useful in treating, preventing, or slowing the progression of diseases requiring 11-beta-hydroxysteroid dehydrogenase type I inhibitor therapy. These novel compounds have the structure: enantiomers, diastereomers, solvates, or salts thereof, wherein A, W, X and Z are defined herein.

Pyrrolidine gpr40 modulators

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.

INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS

The present invention provides compounds of Formula (Ia) or (Ib): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV- containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αV-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

Bicyclic heteroaryl compounds as gpr119 modulators.

La presente invención se refiere a compuestos novedosos de estructura de Fórmula I: (Ver Formula) o un enantiómero, diastereómero, tautómero, profármaco o sal de los mismos, en donde A, D, D1, E, J, L, n, Q, R2 y R4 están definidos en el presente documento, que son moduladores del receptor acoplado a proteína G GPR119. Los moduladores del receptor acoplado a proteína G GPR119 son útiles para tratar, prevenir o ralentizar la progresión de enfermedades que necesitan de terapia moduladora del receptor acoplado a proteína G GPR119. Por tanto, la descripción también se refiere a composiciones que comprenden estos compuestos novedosos y a procedimientos para tratar enfermedades o afecciones relacionadas con la actividad del receptor acoplado a proteína G GPR119 mediante el uso de cualquiera de estos compuestos novedosos o una composición que comprende cualquiera de estos compuestos novedosos.

3-substituted propionic acids as alpha v integrin inhibitors

RESUMEN DE LA INVENCIÓN La presente invención se refiere a compuestos de la Fórmula (I): (I), o estereoisómeros, tautómeros o sales farmacéuticamente aceptables o solvatos de los mismos, en donde todas las variables son como se definen en la presente. Estos compuestos son antagonistas para las integrinas que contienen V. Esta invención también se refiere a composiciones farmacéuticas que comprenden estos compuestos y métodos para tratar una enfermedad, trastorno o afección asociados a la desregulación de integrinas que contienen αv, tales como fibrosis patológica, rechazo al trasplante, cáncer, osteoporosis y trastorno inflamatorio, mediante el uso de compuestos y composiciones farmacéuticas. SUMMARY OF THE INVENTION The present invention relates to compounds of the Formula (I): (I), or stereoisomers, tautomers or pharmaceutically acceptable salts or solvates thereof, wherein all variables are as defined herein. These compounds are antagonists for integrins that contain V. This invention also relates to pharmaceutical compositions comprising these compounds and methods for treating a disease, disorder or condition associated with the deregulation of integrins containing αv, such as pathological fibrosis, transplant rejection, cancer, osteoporosis and inflammatory disorder, by means of use of compounds and pharmaceutical compositions.

Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method

Formula, wherein Z1 is (CH2)q or C=O; Z2 is (CH2)p or C=O; D is -CH= or C=O or (CH2)m where m is 0, 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2; q = 0, 1 or 2; Q is C or N; A is (CH2)x where x is 1 to 5, or A is (CH2)x1, where x1 is 1 to 5 with an alkenyl bond or an alkynyl bond embedded anywhere in the chain, or A is -(CH2)x2-O-(CH2)x3 - where x2 is 0 to 5 and x3 is 0 to 5, provided that at least one of x2 and x3 is other than 0; B is a bond or is (CH2)x4 where x4 is 1 to 5; X is CH or N; X2 is C, N, O or S; X3 is C, N, O or S; X4 is C, N, O or S; X5 is C, N, O or S; X6 is C, N, O or S; provided that at least one of X2, X3, X4 X5 and X6 is N; and at least one of X2, X3, X4 X5 and X6 is C. R1 is H or alkyl; R2 is H, alkyl, alkoxy, halogen, amino, substituted amino or cyano; R2a, R2b and R2c may be the same or different and are selected from H, alkyl, alkoxy, halogen, amino, substituted amino or cyano; and R3, E, Z and Y are as defined herein.

3-substituted propionic acids as alpha v integrin inhibitors

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to α ν - containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of ay- containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors

Bicyclic heteroaryl compounds as gpr119 modulators

Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, D, Di, E, J, L, n, Q, R2 and R4 are defined herein, are provided which are GPR119 G protein- coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

3-substituted propionic acids as αV integrin inhibitors

The present invention provides compounds of Formula (I):or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to αV-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of αv-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

3-substituted propionic acids as alpha v integrin inhibitors

The present invention provides compounds of Formula (I): Formula (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds are antagonists to av-containing integrins. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with dysregulation of av-containing integrins, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors

Substituted hertocyclic derivatives useful as antidiabetic and antiobesity agents and method

Formula, wherein Z1 is (CH2)q or C=O; Z2 is (CH2)p or C=O; D is -CH= or C=O or (CH2)m where m is 0, 1, 2 or 3; n = 0, 1 or 2; p = 1 or 2; q = 0, 1 or 2; Q is C or N; A is (CH2)x where x is 1 to 5, or A is (CH2)x1, where x1 is 1 to 5 with an alkenyl bond or an alkynyl bond embedded anywhere in the chain, or A is -(CH2)x2-O-(CH2)x3 - where x2 is 0 to 5 and x3 is 0 to 5, provided that at least one of x2 and x3 is other than 0; B is a bond or is (CH2)x4 where x4 is 1 to 5; X is CH or N; X2 is C, N, O or S; X3 is C, N, O or S; X4 is C, N, O or S; X5 is C, N, O or S; X6 is C, N, O or S; provided that at least one of X2, X3, X4 X5 and X6 is N; and at least one of X2, X3, X4 X5 and X6 is C. R1 is H or alkyl; R2 is H, alkyl, alkoxy, halogen, amino, substituted amino or cyano; R2a, R2b and R2c may be the same or different and are selected from H, alkyl, alkoxy, halogen, amino, substituted amino or cyano; and R3, E, Z and Y are as defined herein.

Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method

Pyrrolidine GPR40 modulators

The present invention provides compounds of Formula (I): or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are GPR40 G protein-coupled receptor modulators which may be used as medicaments.