Selective androgen receptor modulators and methods of use thereof
This invention provides a class of androgen receptor targeting agents. The agents define a new subclass of compounds, which are selective androgen receptor modulators (SARM).
1 . A selective androgen receptor modulator (SARM) compound represented by the structure of formula (IIA):
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, or SnR 3 ;
R is an alkyl group or OH; and
Q is CN.
2 . A selective androgen receptor modulator (SARM) compound represented by the structure of formula (IIA):
wherein
X is O;
Z is NO 2 , CN, COR, or CONHR;
Y is I, CF 3 , Br, Cl, or SnR 3 ;
R is an alkyl group or OH; and
Q is CN;
or its analog, isomer, metabolite, derivative, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, N-oxide, hydrate or any combination thereof.
3 . The selective androgen modulator compound according to claim 1 , wherein Z is NO 2 .
4 . The selective androgen modulator compound according to claim 1 , wherein Z is CN.
5 . The selective androgen modulator compound according to claim 1 , wherein Y is CF 3 .
6 . The selective androgen modulator compound according to claim 1 , wherein Q is CN.
7 . The selective androgen modulator compound according to claim 1 , wherein Z is NO 2 , Y is CF 3 , and Q is CN.
8 . The selective androgen modulator compound according to claim 1 , wherein Z is CN, Y is CF 3 , and Q is CN.
9 . A selective androgen receptor modulator (SARM) compound represented by the structure of formula (III):
10 . A composition comprising the selective androgen receptor modulator compound of claims 1 or 9 , and/or its analog, isomer, metabolite, derivative, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, N-oxide, hydrate or any combination thereof; and a suitable carrier or diluent.
11 . A pharmaceutical composition comprising an effective amount of the selective androgen receptor modulator compound of claims 1 or 9 , and/or its analog, isomer, metabolite, derivative, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, N-oxide, hydrate; and a pharmaceutically acceptable carrier, diluent or salt.
12 . A method of binding a selective androgen receptor modulator compound to an androgen receptor, comprising the step of contacting the androgen receptor with the selective androgen receptor modulator compound of claim 1 and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, hydrate, N-oxide or any combination thereof, in an amount effective to bind the selective androgen receptor modulator compound to the androgen receptor.
13 . A method of contraception in a male subject, comprising the step of administering to said subject the selective androgen receptor modulator compound of claim 1 and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, hydrate, N-oxide or any combination thereof, in an amount effective to suppress sperm production in said subject, thereby effecting contraception in said subject.
14 . A method of hormone therapy comprising the step of contacting an androgen receptor of a subject with the selective androgen receptor modulator compound of claim 1 and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, hydrate, N-oxide or any combination thereof, in an amount effective to effect a change in an androgen-dependent condition.
15 . A method of treating a subject suffering from prostate cancer, comprising the step of administering to said subject the selective androgen receptor modulator compound of claim 1 and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, hydrate, N-oxide or any combination thereof, in an amount effective to treat prostate cancer in said subject.
16 . A method of delaying the progression of prostate cancer in a subject suffering from prostate cancer, comprising the step of administering to said subject the selective androgen receptor modulator compound of claim 1 and/or its analog, derivative, isomer, metabolite, pharmaceutically acceptable salt, pharmaceutical product, polymorph, crystal, impurity, hydrate, N-oxide or any combination thereof, in an amount effective to delay the progression of prostate cancer in said subject.