Patent ID: 6476016
Filing Date: 2002-11-05
Classification: A61P,C07D

Abstract:
A compound of Formula I: or a hydrate or pharmaceutically acceptable salt thereof; wherein:W is hydrogen, R1, R1OCO, R1CO, R1(CH2)sNHCO, or (R1)2CH(CH2)sNHCO, wherein s is 0-4; R1 is R2, R2(CH2)tC(R12)2, where t is 0-3, and each R12 can be the same or different, (R2)(OR12)CH(CH2)p, where p is 1-4, (R2)2(OR12)C(CH2)p, where p is 1-4, R2C(R12)2(CH2)t, wherein t is 0-3, each R12 can be the same or different, wherein (R12)2 can also form a ring with C represented by C3-7 cycloalkyl, R2CF2C(R12)2(CH2)q, wherein q is 0-2, and each R12 can be the same or different, wherein (R12)2, can also form a ring with C represented by C3-7 cycloalkyl, R2CH2C(R12)2(CH2)q, wherein q is 0-2, and each R12 can be the same or different, wherein (R12)2 can also form a ring with C represented by C3-7 cycloalkyl, (R2)2CH(CH2)r, where r is 0-4and each R2 can be the same or different, and wherein (R2)2 can also form a ring with CH represented by C3-7 cycloalkyl, C7-12 bicyclic alkyl, C10-16 tricyclic alkyl or a 5- to 7-membered mono- or 9- or 10- membered bicyclic heterocyclic ring which is selected from the group consisting of piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, R2O(CH2)p, wherin p is 2-4, (R2)2CF(CH2)r, wherein r is 0-4 and each R2 can be the same or different, wherein (R2)2 can also form a ring with C represented by C3-7 cycloalkyl, C7-2 bicyclic alkyl, C10-16 tricyclic alkyl, or a 5- to 7-membered mono- or 9- or 10- membered bicyclic heterocyclic ring which is selected from the group consisting of piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, R2CF2C(R12)2; R2 is phenyl, naphthyl, or biphenyl, each of which is unsubstituted or substituted with one or more of C1-4 alkyl, C1-4 alkoxy, halogen, hydroxy, CF3, OCF3, COOH, CONH2, or SO2NH2, a 5- to 7-membered mono- or a 9- to 10-membered bicyclic heterocyclic ring or non-heterocyclic ring which can be saturated or unsaturated, wherein the heterocyclic ring is selected from the group consisting of piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, each of which is optionally substituted with halogen or hydroxy, and wherein the heterocyclic or non-heterocyclic ring is unsubstituted or substituted with halogen or hydroxy, C1-7 alkyl, unsubstituted or substituted with one or more of hydroxy, COOH, amino, aryl, C3-7 cycloalkyl, CF3, N(CH3)2, or C1-3 alkylaryl, CF3, C3-7 cycloalkyl, unsubstituted or substituted with aryl, C7-12 bicyclic alkyl, or C10-16 tricyclic alkyl; R3 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, C2-6 alkynyl, optionally substituted C6-10 aryl, optionally substituted C6-10 ar(C1-6)alkyl, trifluoromethyl, halogen, C1-6 hydroxyalkyl, cyano, nitro, carboxamido, â€”CO2Rx, â€”CH2ORx or â€”ORx, where Rx, in each instance, is independently one of hydrogen, C1-6 alkyl or C3-7 cycloalkyl wherein said alkyl or cycloalkyl groups may optionally have one or more unsaturations; R4 is hydrogen or halogen; R12 is hydrogen phenyl, naphthyl, or biphenyl, each of which is unsubstituted with one or more of C1-4 alkyl, C1-4 alkoxy, halogen, hydroxy, CF3, OCF3, COOH, or CONH2, a 5- to 7-membered mono- or a 9- to 10-membered bicyclic heterocyclic ring which is selected from the group consisting of piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piperidonyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, thiadiazoyl, benzopyranyl, benzothiazolyl, benzoxazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, and oxadiazolyl, C1-4 alkyl, unsubstituted or substituted with one or more of hydroxy, COOH, amino, or aryl, CF3, C3-7 cycloalkyl, C7-12 bicyclic alkyl, or C10-16 tricyclic alkyl; R5 is hydrogen, C1-4 alkyl, or C2-4 alkenyl; A is one of Ra, Rb and Rc are independently hydrogen, alkyl, hydroxy, alkoxy, aryloxy, aralkoxy, alkoxycarbonyloxy, cyano or â€”CO2Rw, where Rw is alkyl, cycloalkyl, phenyl, benzyl, where Rd and Re are independently hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, Rf is hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, Rg is hydrogen, C1-6 alkyl, C2-6 alkenyl or phenyl, and Rh is aralkyl or C1-6 alkyl; each n is from zero to 4; each m is from zero to 4; and each j is from zero to 4; provided that n, m and j are not all zero.