Pan-antagonists for the androgen receptor and androgen receptor mutants associated with anti-androgen withdrawal
Disclosed herein are novel antagonists of the androgen receptor and androgen receptor mutations associated with clinical failure of currently prescribed anti-androgens and use of said antagonists in the treatment of conditions associated with inappropriate activation of the androgen receptor.
1. A compound of the formula:
wherein R 1 is hydrogen, fluorine, chlorine, bromine, cyano, hydroxy, methyl acrylate, or C 1 -C 6 alkyl optionally substituted with hydroxy;
R 2 is hydrogen, hydroxy, fluoro, chloro, cyano, C 1 -C 5 alkanoate, C 1 -C 5 alkylamino, or
C 1 -C 6 alkyl optionally substituted with hydroxy or acrylate; and
R 3 is hydrogen, C 1 -C 6 alkyl, fluoro, chloro, bromo, or cyano.
2. The compound of claim 1 , selected from the group consisting of:
3. A compound of the formula:
wherein R 4 is phenyl optionally substituted with hydroxy; C 1 -C 6 phenylalkyl; or benzyl optionally substituted with hydroxy, C 1 -C 6 alkoxy optionally substituted with methoxy or cyano, C 1 -C 6 alkyl, C 1 -C 5 alkanoate, or C 1 -C 5 alkylamine.
4. The compound of claim 3 , selected from the group consisting of:
5. A pharmaceutical composition comprising a compound of claim 1 or 3 .
6. A pharmaceutical composition comprising a compound of claim 2 or 4 .