4-Aza-17-substituted-5-alpha-androstan-3-one, their A and D homo analogs, process for their preparation and pharmaceutical compositions containing them.

摘要

4-Aza-17-substituted-5 alpha -androstan-3-ones and their A- and D- homo analogs of the formula: <CHEM> where Formula (I) may also have the structure of partial Formulas (II) and or (III); wherein, A is (1) - CH2 - CH2 -; (2) - CH = CH -; <CHEM> or <CHEM> B is (1) <CHEM> where R<1> is, (a) hydrogen; (b) methyl or ethyl; (c) ethenyl; (d) ethynyl; (e) NR<2>R<3> where R<2> and R<3> are hydrogen or methyl; (f) cyano; or <CHEM> where X<(-)> is any anion and R<4> is , (a) OR<5 >where R<5> is C1-4 alkyl; or (b) NR<6>R<7>, where R<6> and R<7> are hydrogen or methyl; R min is hydrogen or methyl; R sec is hydrogen or beta -methyl; R''' is B-methyl or hydroxy; Z is (1) oxo ; (2) beta -hydrogen and alpha -hydroxy; or alpha -hydrogen or alpha -hydroxyl and (3) (Y)n Q where n = 0 or 1, Y is a straight or branched hydrocarbon chain of 1 to 12 carbon atoms and Q is (a) <CHEM> , where R<8> is, (i) hydrogen, (ii) hydroxyl, (iii) C1-4 alkyl (iv) NR<9> R<1><0>, where R<9> and R<1><0> are each independently selected from hydrogen, C1-4 straight or branched chain alkyl, C3-6 cycloalkyl, phenyl; or R<9>9 and R<1><0> taken together with the nitrogen to which they are attached represent a 5-6 membered saturated ring comprising up to one other heteratom selected from oxygen and nitrogen. (v) OR<1><1>, where R<1><1> is M, where M is hydrogen or alkali metal, or C1-18 straight or branched chain alkyl; benzyl; or (b) OR<1><2>, where R<1><2> is, (i) C1-20 alkylcarbonyl , (ii) phenyl C1-6 alkylcarbonyl, (iii) C5-10 cycloalkylcarbonyl, (iv) benzoyl, or (v) C1-8 alkoxycarbonyl; (4) <CHEM> where the dashed bond replaced the 17 alpha hydrogen; (5) NH@-R<1><3>, where R<1><3>, is (a) C1-12 alkyl; or (b) NR<9>NR<1><0>; (6) cyano; or (7) tetrazolyl; and pharmaceutically acceptable salts of the above compounds; active as testosterone 5 alpha -reductase inhibitors, and thus useful topically for treatment of acne, seborrhea, female hirsutism and male pattern baldness, and systemically in treatment of benign prostatic hypertrophy, breast carcinoma, and prostate carcinoma.