Patent ID: 6765009
Filing Date: 2004-07-20
Classification: A61P,C07D

Abstract:
A 1,4-disubstituted benzo-fused compound of the formula (I): wherein:ring A is: fused saturated or unsaturated ring containing 3-5 carbon atoms wherein ring A or the phenyl ring to which it is fused is optionally substituted by one or more a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-6 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl, phenylsulfonyl, hydroxy, amino, mono- or di-(C1-4 alkyl)amino, mono- or di-(C1-4 alkyl)amino-S(O)2, cyano, nitro or H2NSO2;G is: phenyl, naphthyl, benzocyclobutanyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl, benzocycloheptenyl, indanyl, indenyl;wherein G is substituted by one R3 and further substituted by one or more R1 or R2;L is: a) â€”Oâ€”; â€”NHâ€”; >C(O); >C(S); C1-10 saturated or unsaturated branched or unbranched carbon chain; wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m; and wherein said L is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino; or b) >CRxRy wherein Rx and Ry are each independently hydrogen, C1-4alkyl, heterocycleC0-4 alkyl, heteroarylC0-4 alkyl or arylC0-4 alkyl; Q is: pyrimidinyl, optionally substituted with one to three C1-6 alkyl, phenyl, C1-6 alkoxy or hydroxy; R1 is independently: C3-10 branched or unbranched alkyl optionally partially or fully halogenated, and optionally substituted with one to three C3-10 cycloalkyl, hydroxy, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl; each of the aforementioned being optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl which is optionally partially or fully halogenated, C3-8 cycloalkyl, C5-8 cycloalkenyl, hydroxy, cyano, C1-3 alkoxy which is optionally partially or fully halogenated and NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, which are optionally partially or fully halogenated and optionally substituted with one to three C1-3 alkyl groups optionally partially or fully halogenated, cyano, hydroxyC1-3 alkyl or aryl;C3-10 branched or unbranched alkenyl optionally partially or fully halogenated, and optionally substituted with one to three C1-5 branched or unbranched alkyl, phenyl, naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl or isothiazolyl, each of the aforementioned are optionally substituted with 1 to 5 halogen, C1-6 branched or unbranched alkyl optionally partially or fully halogenated, cyclopropyl, cyclobutyl, cyclopentanyl, cyclohexanyl, cycloheptanyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl, hydroxy, cyano, C1-3 alkoxy optionally partially or fully halogenated, NH2C(O) or mono- or di(C1-3)alkylaminocarbonyl;cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl, each optionally substituted with one to three C1-3 alkyl groups;N-morpholinyl;cyano, halogen;methoxycarbonyl, ethoxycarbonyl or propoxycarbonyl;silyl containing three C1-4 independently branched or unbranched alkyl groups optionally partially or fully halogenated;C1-6 branched or unbranched alkyl-C(O), C1-6 branched or unbranched-S(O)m;C2-6 alkynyl branched or unbranched carbon chain optionally partially or fully halogenated, wherein one or more methylene groups are optionally replaced by O, NH and S(O)m and wherein said alkynyl group is optionally independently substituted with 0-2 oxo groups, pyrroldinyl, pyrrolyl, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, nitrile, morpholinyl, piperidinyl, piperazinyl, imidazolyl, phenyl, pyridinyl, tetrazolyl, or C1-4 branched or unbranched alkylamino optionally substituted by one or more halogen atoms;R2 is independently: a C1-6 branched or unbranched alkyl optionally partially or fully halogenated, acetyl, aroyl, C1-4 branched or unbranched alkoxy optionally partially or fully halogenated, halogen, methoxycarbonyl or phenylsulfonyl;hydroxy, amino, or mono- or di-(C1-4 alkyl)amino, cyano, halogen;OR5;nitro; ormono- or di-(C1-4 alkyl)amino-S(O)2 optionally partially or fully halogenated, or H2NSO2;each R3 is independently: (J)pâ€”Lâ€²â€”S(O)mâ€”NHâ€” or (J)pâ€”Lâ€²â€”Oâ€”C(O)â€”NHâ€”, wherein for R3: Lâ€² is a bond or C1-10 saturated or unsaturated branched or unbranched carbon chain; wherein one or more carbon atoms are optionally independently replaced by heteroatoms chosen from O, N and S(O)m; and wherein said Lâ€² is optionally substituted with 0-2 oxo groups, one or more C1-4 branched or unbranched alkyl optionally substituted by one or more halogen atoms, hydroxy, amino or imino; J is: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentanyl, bicyclohexanyl or bicycloheptanyl;cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, bicyclohexenyl or bicycloheptenyl;phenyl, naphthyl, morpholinyl, pyridinyl, piperidinyl, piperazinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrrolidinyl, imidazolyl, pyrazolyl, thiazolyl, oxazoyl, [1,3,4]oxadiazol, triazolyl, tetrazolyl, thienyl, furyl, dioxolanyl, tetrahydrofuryl, isoxazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, cinnolinyl, pterindinyl, phthalazinyl, naphthypyridinyl, quinoxalinyl, quinazolinyl, purinyl or indazolyl, a fused aryl selected from benzocyclobutanyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl, benzocycloheptanyl and benzocycloheptenyl, or J is a fused heteroaryl selected from cyclopentenopyridinyl, cyclohexanopyridinyl, cyclopentanopyrimidinyl, cyclohexanopyrimidinyl, cyclopentanopyrazinyl, cyclohexanopyrazinyl, cyclopentanopyridazinyl, cyclohexanopyridazinyl, cyclopentanoquinolinyl, cyclohexanoquinolinyl, cyclopentanoisoquinolinyl, cyclohexanoisoquinolinyl, cyclopentanoindolyl, cyclohexanoindolyl, cyclopentanobenzimidazolyl, cyclohexanobenzimidazolyl, cyclopentanobenzoxazolyl, cyclohexanobenzoxazolyl, cyclopentanoimidazolyl, cyclohexanoimidazolyl, cyclopentanothienyl and cyclohexanothienyl;each J is optionally substituted by one to three R4; each R4 is independently C1-6 alkyl, arylC0-6 alkyl, heterocycleC0-6 alkyl, heteroarylC0-6 alkyl each optionally substituted by halogen, hydroxy, carboxy, oxo, nitro or nitrile, or R4 is amino optionally mono- or di-substituted by C1-6 alkyl, C0-6 alkylaryl, C0-6 alkylheterocycle or C0-6 alkylheteroaryl, halogen, hydroxy, carboxy, oxo, nitro or nitrile;wherein if p is 0, then Lâ€² cannot be a bond;each R5 or R6 is independently: hydrogen, arylC0-3 alkyl optionally subtituted by halogen, C1-3 alkyl or diC1-5 alkyl amino, or R5 or R6 are C1-3 acyl, aroyl or C1-6 branched or unbranched alkyl optionally substituted by C1-5 alkoxy, hydroxy, mono- or di-C1-3alkylaminocarbonyl or mono or diC1-3 alkyl amino wherein said C1-6 alkyl optionally partially or fully halogenated;or R5 and R6 taken together optionally form a heterocyclic or heteroaryl ring;Y, which covalently attached to Q, is a bond, â€”Oâ€”, >C(O), â€”NHâ€”, â€”C(O)â€”NHâ€”, â€”Sâ€”, C1-5 alkyl branched or unbranched, C1-3 alkyl(OH), C2-5 alkenyl, C1-3 acyl, heterocycle selected from morpholinyl, piperzinyl, piperidinyl, pyrrolidinyl or tetrahydrofuryl, heteroaryl selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, pyrazolyl, thienyl, furyl, isoxazolyl, thiazolyl, oxazolyl, triazolyl, tetrazolyl, isothiazolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, benzopyrazolyl, benzothiofuranyl, quinoxalinyl, quinazolinyl or indazolyl or aryl each alkyl, alkenyl, acyl, heterocycle, heteroaryl and aryl are optionally substituted by one to three hydroxy, oxo, C1-4 alkyl, C1-3 alkoxy, C1-4 acyl, C1-5 alkoxycarbonyl, NR5R6 or NR5R6â€”C(O)â€”;wherein each Y is optionally further covalently attached to NR5R6, C1-4 alkyl, C3-7 cycloalkylC0-4 alkyl, C1-4 alkoxy, aryloxy, hydroxy, arylC0-4 alkyl, heteroarylC0-4 alkyl or heterocycleC0-4 alkyl as wherein the heteroaryl and heterocycle moieties are as hereinabove described for Y and the heterocycle, heteroaryl and aryl moieties are optionally substituted by one to three hydroxy, oxo, C1-3 alkyl, C1-3 alkoxy, C1-5 alkoxycarbonyl, NR5R6 or NR5R6â€”C(O)â€”;m, n and p are each independently 0, 1 or 2;X is O or S; andthe pharmaceutically acceptable derivatives thereof.