Selective androgen receptor modulators, analogs and derivatives thereof and uses thereof
This invention provides nuclear hormone receptor binding compounds, compositions comprising the same and methods of uses thereof in treating a variety of diseases or conditions in a subject, including, inter-alia, prostate cancer and/or diseases or disorders of bone and muscle.
1. A compound represented by the structure of formula III:
wherein
X 2 is O, S, SO, S(O)[=CHCH 2 N(CH 3 ) 2 ], SO 2 , NH, NR, NO, C 1-4 alkylene, C(OH)[CH 2 CH 2 N(CH 3 ) 2 ], C(=CHCH 2 N(CH 3 ) 2 ), PO(C 1-4 alkyl), N[CH 2 CH 2 N(CH 3 ) 2 ], NO[CH 2 CH 2 N(CH 3 ) 2 ];
R is NH 2 , OH, CH 3 ;
R 1 is H, halide;
A is (CH 2 ) n ; n is 0 or 1;
R 3 is H, OH or =O;
R 4 is H, oxo (=O), or Q; R 5 is H; or
R 5 and R 4 are H and the carbons to which they are attached are connected by a double bond;
Y and R 2 independently are H, C 1-4 alkyl, CF 3 , CN or halide;
Z is H, CN, NO 2 or halide; and
Q is H, CN, NO 2 , halide, C(O)CH 2 NH 2 , C(O)NH(C 1-4 alkyl), C(O)N(C 1-4 alkyl) 2 , C(O)NH 2 , NH(C 1-4 alkyl), NHC(O)NH 2 , NHCO(C 1-4 alkyl) or NHSO 2 (C 1-4 alkyl).
2. The compound of claim 1 , represented by the structure of formula IV:
wherein R 1 , R 2 , R 3 , R 4 , R 5 , Z, Y, Q and X 2 are as described above for formula III.
3. The compound of claim 2 , wherein Z is CN; Y is CF 3 ; R 3 is OH; R 1 , R 2 , R 4 and R 5 are H; X 2 is O; and Q is CN.
4. The compound of claim 1 , represented by the structure of formula V:
wherein R 1 , R 2 , R 4 , R 5 , Z, Y, Q , are as described above for formula III.
5. The compound of claim 4 , wherein R 1 , R 2 , R 4 and R 5 are H, Z is CN, Y is CF 3 , and Q is CN.
6. The compound of claim 1 , represented by the structure of formula VI:
wherein R 1 , R 2 , Z, Y, Q and X 2 are as described above for formula III.
7. The compound of claim 6 , wherein Z is CN, R 1 is H, R 2 is H, Y is CF 3 , X 2 is O and Q is CN.
8. The compound of claim 1 , represented by the structure of formula VII:
wherein R 1 , R 2 , Z, Y, Q and X 2 are as described above for formula III.
9. The compound of claim 8 , wherein Z is CN, Y is CF 3 , R 1 is H, R 2 is H, X 2 is CH 2 , and Q is CN.
10. The compound of claim 1 , represented by the structure of formula VIII:
wherein R 1 , R 2 , Z, Y, Q , A and X 2 are as described above for formula III.
11. The compound of claim 10 , wherein Z is CN, Y is CF 3 , R 1 and R 2 are H, A is CH 2 , X 2 is O, and Q is CN.
12. A pharmaceutical composition comprising the compound of claim 1 ; and a suitable carrier or diluent.
13. A pharmaceutical composition comprising an effective amount of the compound of claim 1 ; and a pharmaceutically acceptable carrier, diluent or salt.
14. The compound of claim 1 , wherein said compound is an optical isomer, pharmaceutically acceptable salt, pharmaceutical product, N-oxide, hydrate or any combination thereof, wherein said hydrate is hemihydrate, monohydrate, dihydrate, trihydrate or any combination thereof.
15. The composition of claim 12 , wherein said compound is an optical isomer, pharmaceutically acceptable salt, pharmaceutical product, N-oxide, hydrate or any combination thereof, wherein said hydrate is hemihydrate, monohydrate, dihydrate, trihydrate or any combination thereof.