17-hydroxy-4-aza-androstan-3-ones as androgen receptor modulators

A compound of structural formula II:

• or a pharmaceutically acceptable salt thereof wherein
• wherein
• “a” represents a single bond or a double bond;
• R1 is hydrogen, hydroxymethyl, or C1-3 alkyl, wherein alkyl is unsubstituted or substituted with one to seven fluorine atoms;
• R2 is hydrogen, fluorine, or C1-4 alkyl when “a” represents a double bond;
• or two R2 substituents are each independently hydrogen, fluorine, or C1-4 aikyl when “a” represents a single bond;
• R4 is hydrogen, C1-4 alkyl, C2-4 alkenyl, or C2-4 alkynyl;
• R5 and R6 taken together are ═CHaryl, wherein aryl arylmethyl, wherein aryl is selected from the group consisting of phenyl, naphthyl, pyridyl, furanyl, pyrrolyl, thiazolyl, imidazolyl, benzofuranyl, and 1,3-benzodioxolyl, wherein the aryl group is unsubstituted or substituted with one to two groups independently selected from halogen, C1-4 alkyl, C1-4 alkoxy, cyano, trifluoromethyl, and trifluoromethoxy.

The compound selected from the group consisting of:

• 17β-hydroxy-16α-(2-trifluoromethylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(3-trifluoromethylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(4-trifluoromethylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(2-fluorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(3-fluorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(4-fluorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(3-chlorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(4-chlorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(4-trifluoromethoxybenzyl)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(3-methoxybenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-benzyl-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(2-methylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(2-naphthyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16β-(2-methylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16α-(3-methylbenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16β-(4-chlorobenzyl)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-chlorobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-fluorobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-trifluoromethylbenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-trifluoromethylbenzylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-methoxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3,4-methylenedioxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(5-methoxy-3,4-methylenedioxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3,5-difluorobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3,5-dichlorobenzylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3,4-dimethoxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(pyridin-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(pyridin-4-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(furan-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(1-methyl-imidazol-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(piperidin-4-ylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(N-t-butyloxycarbonylpiperidin-4-ylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(1,3-thiazol-2-ylmethylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(benzofuran-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(5-hydroxymethyl-furan-2-ylmethylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(1-methyl-pyrrol-2-ylmethylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(pyrrol-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-ethoxy-pyrimidin-5-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(pyrimidin-5-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-methyl-pyrimidin-5-ylmethylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-trifluoromethoxybenzylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(4-trifluoromethoxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(4-dimethylaminobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(9-methoxy-quinolin-2-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(quinoxalin-6-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(quinoxalin-7-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-hydroxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-hydroxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(4-hydroxybenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(pyridin-3-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(N-methylpiperidin-4-ylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-chloro-4-dimethylaminobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(2-amino-pyridin-3-ylmethylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-carboxymethyl-benzylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-carboxybenzylidene)4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(3-nitrobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• 17β-hydroxy-16-(4-nitrobenzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• and
• 17β-hydroxy-16-(benzylidene)-4-methyl-4-aza-5α-androst-1-en-3-one;
• or a pharmaceutically acceptable salt thereof.