4-aza-17-substituted-5-alpha-androstan-3-one, their a and d homo analogs, process for their preparation and pharmaceutical compositions containing them

Claim 1

A compound of the formula: where Formula (I) may also have the structure of partial Formulas (II) and/or (III); wherein, A is or B is 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 where X e is any anion and R 4 is, (a) OR 5 where R 5 is C 1-4 alkyl; or (b) NR 6 R 7 , where R 6 and R 7 are hydrogen or methyl; R' is hydrogen or methyl; R" is hydrogen or β-methyl; R"' is hydrogen β-methyl or hydroxy; Z is (1) oxo; (2) β-hydrogen and α-hydroxy; or a-hydrogen or a-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 where R 8 is, (i) hydrogen, (ii) hydroxyl, (iii) C 1-4 alkyl (iv) NR 9 R 10 , where R 9 and R 10 are each independently selected from hydrogen, C 1-4 straight or branched chain alkyl, C 3-6 cycloalkyl, phenyl; or R 9 and R 10 taken together with the nitrogen to which they are attached represent a 5-6 membered saturated ring comprising up to one other heteroatom selected from oxygen and nitrogen. (v) OR", where R" is M, where M is hydrogen or alkali metal, or C 1-18 straight or branched chain alkyl; benzyl; or (b) OR 12 , provided that for 17α-OH, n must = 1, where R 12 is, (i) C 1-20 alkylcarbonyl, (ii) phenyl C 1-6 alkylcarbonyl, (iii) C 5-10 cycloalkylcarbonyl, (iv) benozyl, or (v) C 1-8 alkoxycarbonyl; where the dashed bond replaces the 17α hydrogen; provided that for 17a-OH, n must = 1, where R 13 is, (a) C 1-12 alkyl; or (b) NR 9 R 10 ; (6) cyano; or (7) tetrazolyl; and pharmaceutically acceptable salts of the above compounds.

Claim 8

A method of preparing the compound of the formula: comprising the steps of (1) treating pregnenolone with iodine and pyridine to form the corresponding 20-pyridinium iodide derivative of pregnenolone; (2) methanolyzing the product of step (1) to form the methyl ester of 17-carboxy androstenol; (3) treating the product of step (2) with aluminum isopropoxide and cyclohexanone to form methyl-4- androsten-3-one-17-carboxylate; (4) hydrolyzing the product of step (3) to form the corresponding 17-acid compound; (5) treating the product of step (4) with an oxalyl chloride: pyridine complex to form the corresponding 17-acid chloride compound; (6) treating the product of step (5) in situ with diethylamine to form 17β-N,N-diethylcarbamoyl-4- androstan-3-one; (7) oxidizing the product of step (6) with sodium periodate and potassium permanganate in a tert-butanol: water solvent system to form the corresponding 5-oxo-3,5-secoandrostan-3-oic acid compound; (8) treating the product of step (7) with methylamine in ethylene glycol to form 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androstan-3-one; (9) hydrogenating the product of step (8) by treating it with hydrogen under catalytic conditions to form the final product, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one.

Claim 9

A method of preparing the compound of the formula: comprising the steps of (1) treating pregnenolone with iodine and pyridine to form the corresponding 20-pyridinium iodide derivative of pregnenolone; (2) methanolyzing the product of step (1) to form the methyl ester of 17-carboxy androstenol; (3) treating the product of step (2) with aluminum isopropoxide and cyclohexanone to form methyl-4- androsten-3-one-17-carboxylate; (4) hydrolyzing the product of step (3) to form the corresponding 17-acid compound; (5) treating the product of step (4) with an oxalyl chloride: pyridine complex to form the corresponding 17-acid chloride compound; (6) treating the product of step (5) in situ with diethylamine to form 17β-N,N-diethylcarbamoyl-4- androstan-3-one; (7) oxidizing the product of step (6) with sodium periodate and potassium permanganate in a tert-butanol: water solvent system to form the corresponding 5-oxo-3,5-secoandrostan-3-oic acid compound; (8) treating the product of step (7) with methylamine in ethylene glycol to form 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androstan-3-one; (9) hydrogenating the product of step (8) by treating it with hydrogen under catalytic conditions to form the final product, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one.

Claim 10

A method of preparing the compound of the formula: comprising the steps of (1) treating 4-androsten-3-one-17β-carboxylic acid with an oxalyl chloride: pyridine complex to form the corresponding 17-acid chloride; (2) treating the product of step (1) in situ with diethylamine to form 17A-N,N-diethylcarbamoyl-4- androsten-3-one; (3) oxidizing the product of step (2) with sodium periodate and potassium permangenate in a tert-butanol: water solvent system to form the corresponding 5-oxo-3,5-seconandrostan-3-oic acid compound; (4) treating the product of step (3) with methylamine in ethylene glycol to form 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androsten-3-one; (5) hydrogenating the product of step (4) by treating it with hydrogen under catalytic conditions to form the final product, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one.

Claim 11

A method of preparing the compound of the formula: comprising the steps of (1) treating 4-androsten-3-one-17β-carboxylic acid with an oxalyl chloride: pyridine complex to form the corresponding 17-acid chloride; (2) treating the product of step (1) in situ with diethylamine to form 17A-N,N-diethylcarbamoyl-4- androsten-3-one; (3) oxidizing the product of step (2) with sodium periodate and potassium permangenate in a tert-butanol: water solvent system to form the corresponding 5-oxo-3,5-seconandrostan-3-oic acid compound; (4) treating the product of step (3) with methylamine in ethylene glycol to form 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androsten-3-one; (5) hydrogenating the product of step (4) by treating it with hydrogen under catalytic conditions to form the final product, 17β-N,N-diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one.