5 alpha-reductase Inhibitors

摘要

A series of benzoquinolin-3-ones are pharmaceuticals effective in treating conditions consequent on both Type I and Type II 5 alpha -reductase. The compounds have the formula <CHEM> wherein R and R<1> both represent hydrogen or combine to form a bond; R<2> represents hydrogen or C1-C3 alkyl; R<3> represents methyl or ethyl; R<4> and -X-R<5> each occupies one of the 7-, 8-and 9-positions; R<4> represents hydrogen, halo, methyl or ethyl; X represents C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, a bond, -SO-, -SO2-, -CO-Y-(CH2)n-, -Y-CO-(CH2)n, -CO-, -Z-(CH2)n-, or -SO3-; wherein X groups which are not symmetrical may be in either orientation; Y represents -S-, -O-, or -NH-; Z represents -O- or -S-; n represents 0-3; R<5> represents phenyl, naphthalenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, anthracenyl, acenaphthalenyl, thiazolyl, benzimidazolyl, indazolyl, thiophenyl, phenanthrenyl, quinolinyl, fluorenyl, isoquinolinyl, indanyl, benzopyranyl, indolyl, benzisoquinolinyl, benzindolyl, benzothiazolyl, benzothiophenyl, quinoxalinyl, benzoxazolyl, tetrazolyl, naphthothiazolyl, quinazolinyl, thiazolopyridinyl, pyridazinoquinazolinyl, benzisothiazolyl, benzodioxolyl, benzodioxinyl, diphenylmethyl or triphenylmethyl; the above R<5> groups are unsubstituted or substituted with 1-3 groups chosen from the group consisting of halo, trifluoromethyl, trifluoroethoxy, C1-C4 alkyl, trifluoromethoxy, hydroxy, C1-C3 alkoxy, nitro, C1-C3 alkylthio, C1-C6 alkanoyl, phenyl, oxo, phenoxy, phenylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, cyano, amino, C1-C3 alkylamino, diphenylmethylamino, triphenylmethylamino, benzyloxy, benzylthio, (mono-halo, nitro or CF3)benzyl(oxy or thio), di(C1-C3 alkyl, C3-C6 cycloalkyl, or C4-C8 cycloalkylalkyl)amino, (mono-C1-C3 alkyl, C1-C3 alkoxy or halo)-(phenyl, phenoxy, phenylthio, phenylsulfonyl or phenoxysulfonyl), C2-C6 alkanoylamino, benzoylamino, diphenylmethylamino(C1-C3 alkyl), aminocarbonyl, C1-C3 alkylaminocarbonyl, di(C1-C3 alkyl)aminocarbonyl, halo-C1-C6 alkanoyl, aminosulfonyl, C1-C3 alkylaminosulfonyl, di(C1-C3 alkyl)aminosulfonyl, phenyl(oxy or thio)(C1-C3 alkyl), (halo, C1-C3 alkyl or C1-C3 alkoxy)phenyl(oxy or thio) (C1-C3 alkyl), benzoyl, or (amino, C1-C3 alkylamino or di(C1-C3 alkyl)amino)(C1-C3 alkyl); or an above R<5> group is substituted with a morpholino(C1-C3 alkyl) group, a phenyl(C1-C3 alkyl)piperidinyl group, a phenyl(C1-C3 alkyl)-Piperidinylaminocarbonyl group, a C2-C6 alkanoylaminothiophenyl group, or a (amino, C1-C3 alkylamino or di(C1-C3 alkyl)amino)naphthalenylsulfonylamino group; or R<5> is a perhalophenyl group; or a pharmaceutically acceptable salt thereof.