Novel non-steroidal compounds as androgen receptor modulators

Compounds of the formula (II)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof,
• wherein
• m is an integer from 1 to 4;
• n is an integer from 0 to 4;
• A is carbon or nitrogen;
• R6 is hydroxyl, acyloxyl, carboxyl or carboxylate;
• R4 is phenyl which is substituted with 1-5 R5, or naphthalene-1-yl, naphthalene-2-yl, benzyl, phenethyl or 3-phenylpropyl which is substituted with 0-5 R5;
• provided that
• when A is carbon, m is 1, n is 0, and R6 is hydroxyl occupying site 4 of ring X, then R4 cannot be 4-methoxyphenyl, 4-chlorophenyl, 2-fluorophenyl, 2,4-dichlorophenyl, 2,6-dichlorophenyl or;
• when A is carbon, m is 3, n is 0, and R6 is carboxylic acid methyl ester occupying site 6 of ring X, then R4 cannot be 4-chlorophenyl or 4-(1-methylethyl)phenyl;
• when A is carbon, m is 4, n is 0, and R6 is carboxylic acid methyl ester occupying site 6 or 7 of ring X, then R4 cannot be 4-chlorophenyl;

Compounds of the formula (I)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof,
• wherein
• A is carbon or nitrogen;
• R1 is hydrogen or alkyl;
• R2 is hydrogen, alkyl or phenyl, provided that R1 and R2 cannot simultaneously be hydrogen;
• R3 is alkyl or benzyl and may form with R1 a monocyclic aliphatic structure, which may be substituted with a side chain of the formula
• wherein n is an integer from 0 to 4 and R6 is hydroxyl, acyloxyl, carboxyl or carboxylate,
• provided that R2 and R3 cannot simultaneously be alkyl;
• R4 is phenyl which is substituted with 1-5 R5, or naphthalene-1-yl, naphthalene-2-yl, benzyl, phenethyl or 3-phenylpropyl which is substituted with 0-5 R5;
• R5 is selected from the group consisting of halogen, nitro, cyano, alkyl, hydroxyl or lower alkoxyl, provided that when R4 is phenyl there can not be more than one hydroxyl or lower alkoxyl simultaneously present as R5 and that alkyl or alkoxyl groups may be further substituted by the above mentioned groups provided that
• when A is carbon, R1 is hydrogen, R2 is methyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 2-, 3- or 4-chlorophenyl, 4-benzonitrile, or naphthalene-2-yl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 4-chlorophenyl or 4-nitrophenyl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is methyl, then R4 cannot be phenethyl, 3-phenyl-propyl, 2-(2-, 3- or 4-hydroxyphenyl)-ethyl or 3-(4-hydroxy-phenyl)propyl;
• for use as pharmaceuticals.

A pharmaceutical composition comprising a compound of the formula (I)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof,
• wherein
• A is carbon or nitrogen;
• R1 is hydrogen or alkyl;
• R2 is hydrogen, alkyl or phenyl, provided that R1 and R2 cannot simultaneously be hydrogen;
• R3 is alkyl or benzyl and may form with R1 a monocyclic aliphatic structure, which may be substituted with a side chain of the formula
• wherein n is an integer from 0 to 4 and R6 is hydroxyl, acyloxyl, carboxyl or carboxylate,
• provided that R2 and R3 cannot simultaneously be alkyl;
• R4 is phenyl which is substituted with 1-5 R5, or naphthalene-1-yl, naphthalene-2-yl, benzyl, phenethyl or 3-phenylpropyl which is substituted with 0-5 R5;
• R5 is selected from the group consisting of halogen, nitro, cyano, alkyl, hydroxyl and lower alkoxyl, provided that when R4 is phenyl there can not be more than one hydroxyl or lower alkoxyl simultaneously present as R5 and that alkyl or alkoxyl groups may be further substituted by the above mentioned groups provided that
• when A is carbon, R1 is hydrogen, R2 is methyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 2-, 3- or 4-chlorophenyl, 4-benzonitrile, or naphthalene-2-yl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 4-chlorophenyl or 4-nitrophenyl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is methyl, then R4 cannot be phenethyl, 3-phenyl-propyl, 2-(2-, 3- or 4-hydroxyphenyl)-ethyl or 3-(4-hydroxy-phenyl)propyl;
• in association with a pharmaceutically acceptable carrier.

Compounds of the formula (I)

• or stereoisomers, pharmaceutically acceptable salts or prodrug forms thereof,
• wherein
• A is carbon or nitrogen;
• R1 is hydrogen or alkyl;
• R2 is hydrogen, alkyl or phenyl, provided that R1 and R2 cannot simultaneously be hydrogen;
• R3 is alkyl or benzyl and may form with R1 a monocyclic aliphatic structure, which may be substituted with a side chain of the formula
• wherein n is an integer from 0 to 4 and R6 is hydroxyl, acyloxyl, carboxyl or carboxylate,
• provided that R2 and R3 cannot simultaneously be alkyl;
• R4 is phenyl which is substituted with 1-5 R5, or naphthalene-1-yl, naphthalene-2-yl, benzyl, phenethyl or 3-phenylpropyl which is substituted with 0-5 R5;
• R5 is selected from the group consisting of halogen, nitro, cyano, alkyl, hydroxyl and lower alkoxyl, provided that when R4 is phenyl there can not be more than one hydroxyl or lower alkoxyl simultaneously present as R5 and that alkyl or alkoxyl groups may be further substituted by the above mentioned groups, provided that
• when A is carbon, R1 is hydrogen, R2 is methyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 2-, 3- or 4-chlorophenyl, 4-benzonitrile, or naphthalene-2-yl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is benzyl, then R4 cannot be 2-, 3- or 4-methoxyphenyl, 2-fluorophenyl, 4-chlorophenyl or 4-nitrophenyl;
• when A is carbon, R1 is hydrogen, R2 is phenyl and R3 is methyl, then R4 cannot be phenethyl, 3-phenyl-propyl, 2-(2-, 3- or 4-hydroxyphenyl)-ethyl or 3-(4-hydroxy-phenyl)propyl;
• for use in a method for treating disease states, disorders or conditions alleviated by compounds having androgen, antiandrogen or androgen receptor modulator activity.