Patent ID: 6228881
Filing Date: 2001-05-08
Classification: A61P,C07D

Abstract:
A compound of the formula I ##STR32##wherein:the heterocyclic moiety ##STR33##is selected from the group consisting of: ##STR34##X is S, O or NR.sub.6 ;Y is CHR.sub.7 or N--H;R.sub.1 is selected from the group consisting of:(a) C.sub.3-10 branched alkyl, which is optionally partially or fully halogenated, and optionally substituted with one to three phenyl, naphthyl or heteroaryl independently selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, each phenyl, naphthyl or heteroaryl group being substituted with 0 to 5 groups selected from halogen, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C.sub.3-8 cycloalkyl, C.sub.5-8 cycloalkenyl, hydroxy, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, aminocarbonyl and di(C.sub.1-3)alkylaminocarbonyl;(b) a cycloalkyl group selected from cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which cycloalkyl group is optionally partially or fully halogenated and which is optionally substituted with one to three C.sub.1-3 alkyl groups, or an analog of said cycloalkyl group wherein instead of one to three ring methylene groups there are groups independently selected from O, S, CHOH, >C.dbd.O, >C.dbd.S and NH;(c) C.sub.3-10 branched alkenyl which is optionally partially or fully halogenated, and which is optionally substituted with one to three groups independently selected from C.sub.1-5 branched or unbranched alkyl, phenyl, naphthyl or heteroaryl independently selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, and each phenyl, naphthyl or heteroaryl group being substituted with 0 to 5 groups selected from halogen, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, hydroxy, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, aminocarbonyl and mono- or di(C.sub.1-3)alkylaminocarbonyl;(d) a cycloalkenyl group selected from cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein said cycloalkenyl group is optionally substituted with one to three C.sub.1-3 alkyl groups;(e) cyano; and,(f) an alkoxy carbonyl group selected from methoxycarbonyl, ethoxycarbonyl and propoxycarbonyl;R.sub.2 is selected from the group consisting of hydrogen, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, acetyl, benzoyl and phenylsulfonyl;R.sub.3 is selected from the group consisting of:a) phenyl, naphthyl and heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl, wherein each phenyl, naphthyl or heteroaryl group is optionally substituted with one to five groups independently selected from C.sub.1-6 branched or unbranched alkyl, phenyl, naphthyl, heteroaryl selected from the group set forth immediately above, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, phenyl C.sub.1-5 alkyl, naphthyl C.sub.1-5 alkyl, halo, hydroxy, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteraryloxy wherein the heteroaryl moiety is selected from the group set forth above in this subparagraph, nitro, amino, mono- or di-(C.sub.1-3)alkylamino, phenylamino, naphthylamino, heteroarylamino wherein the heteroaryl moiety is selected from the group set forth above in this subparagraph, aminocarbonyl, a mono- or di-(C.sub.1-3)alkyl aminocarbonyl, C.sub.1-4 branched or unbranched alkyl oxycarbonyl, C.sub.1-5 alkylcarbonyl C.sub.1-4 branched or unbranched alkyl, amino C.sub.1-5 alkyl, mono- or di-(C.sub.1-3)alkylamino(C.sub.1-5)alkyl, aminosulfonyl, di-(C.sub.1-3)alkylaminosulfonyl;b) fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, and fused heteroaryl selected from cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene, wherein the fused aryl or fused heteroaryl ring is substituted with 0 to 3 groups independently selected from phenyl, naphthyl and heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, halo, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, heteroaryloxy wherein the heteroaryl moiety is selected from the group set forth above in this subparagraph, nitro, amino, mono- or di-(C.sub.1-3)alkylamino, phenylamino, naphthylamino, heteroarylamino wherein the heteroaryl moiety is selected from the group set forth above in this subparagraph, aminocarbonyl, a mono- or di-(C.sub.1-3)alkyl aminocarbonyl, C.sub.1-4 branched or unbranched alkyl oxycarbonyl, C.sub.1-5 alkylcarbonyl C.sub.1-4 branched or unbranched alkyl, amino C.sub.1-5 alkyl, mono- or di-(C.sub.1-3)alkylamino(C.sub.1-5)alkyl, aminosulfonyl, di-(C.sub.1-3)alkylaminosulfonyl;c) a cycloalkyl group selected from cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which cycloalkyl group is optionally partially or fully halogenated and which is optionally substituted with one to three C.sub.1-3 alkyl groups;d) a cycloalkenyl group selected from cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, wherein said cycloalkenyl group is optionally substituted with one to three C.sub.1-3 alkyl groups; and,e) acetyl, benzoyl and phenylsulfonyl;or R.sub.1 and R.sub.2 taken together optionally form a fused phenyl ring;R.sub.5 is selected from the group consisting of:a) phenyl, naphthyl and heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzpyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl and indazolyl, wherein each phenyl, naphthyl or heteroaryl group optionally bears one to five groups selected from phenyl, naphthyl and heteroaryl wherein each heteroaryl moiety is independently selected from the group defined above in this subparagraph, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl, bicycloheptanyl, halo, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, nitro, amino, mono- or di-(C.sub.1-3) alkylamino, phenylamino, naphthylamino, aminocarbonyl, mono- or di-(C.sub.1-3) alkylaminocarbonyl, amino(C.sub.1-5)alkyl or alkenyl, di-(C.sub.1-3)alkylamino(C.sub.1-5)alkyl or alkenyl, phenylamino(C.sub.1-3)alkyl or alkenyl, naphthylamino(C.sub.1-3)alkyl or alkenyl, phenylamido(C.sub.1-3)alkyl or alkenyl, naphthylamido(C.sub.1-3)alkyl or alkenyl, phenyl(C.sub.1-5)alkyl or alkenyl and naphthyl(C.sub.1-5)alkyl or alkenyl;b) fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, and fused heteroaryl selected from cyclopentenopyridine, cyclohexanopyridine, cyclopentanopyrimidine, cyclohexanopyrimidine, cyclopentanopyrazine, cyclohexanopyrazine, cyclopentanopyridazine, cyclohexanopyridazine, cyclopentanoquinoline, cyclohexanoquinoline, cyclopentanoisoquinoline, cyclohexanoisoquinoline, cyclopentanoindole, cyclohexanoindole, cyclopentanobenzimidazole, cyclohexanobenzimidazole, cyclopentanobenzoxazole, cyclohexanobenzoxazole, cyclopentanoimidazole, cyclohexanoimidazole, cyclopentanothiophene and cyclohexanothiophene, wherein the fused aryl or fused heteroaryl ring bears 0 to 3 groups selected from phenyl, naphthyl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, halo, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy, nitro, amino, mono- or di-(C.sub.1-3) alkylamino, phenylamino, naphthylamino, aminocarbonyl, mono- or di-(C.sub.1-3) alkylaminocarbonyl, amino(C.sub.1-5)alkyl or alkenyl, di-(C.sub.1-3)alkylamino(C.sub.1-5)alkyl or alkenyl, phenylamino(C.sub.1-3)alkyl or alkenyl, naphthylamino(C.sub.1-3)alkyl or alkenyl, phenylarnido(C.sub.1-3)alkyl or alkenyl, naphthylamido(C.sub.1-3)alkyl or alkenyl, phenyl(C.sub.1-5)alkyl or alkenyl and naphthyl(C.sub.1-5)alkyl or alkenyl; and,c) cycloalkyl selected from cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl and bicycloheptanyl, which cycloalkyl group is optionally partially or fully halogenated and which is optionally substituted with one to three C.sub.1-3 alkyl groups;d) cycloalkenyl selected from cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl and bicycloheptenyl, which cycloalkenyl group is optionally partially or fully halogenated and which is optionally substituted with one to three C.sub.1-3 alkyl groups; ande) phenyl(C.sub.1-5 branched or unbranched)alkyl, and naphthyl(C.sub.1-5 branched or unbranched)alkyl, wherein the phenyl or naphthyl ring is substituted with 0 to 5 groups selected from the group consisting of phenyl, naphthyl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl and isothiazolyl, C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, halo, cyano, C.sub.1-3 alkyloxy which is optionally partially or fully halogenated, phenyloxy, naphthyloxy or heteroaryloxy wherein the heteroaryl moiety is as defined above in this subparagraph;R.sub.6 is hydrogen, cyano or C.sub.1-6 branched or unbranched alkyl which is optionally partially or fully halogenated; and,R.sub.7 is hydrogen or C.sub.1-6 branched or unbranched alkyl, which is optionally partially or fully halogenated;or a tautomer or pharmaceutically acceptable salt thereof.