Prostate cancer treatment
View Patent ↗The instant invention provides potent antiandrogen compounds, such as 3β-acetoxyandrost-1,5-diene-17-ethylene ketal and 3β-hydroxyandrost-1,5-diene-17-ethylene ketal, and methods for their use in the prevention and treatment of biological conditions mediated by androgen receptors. Thus, for example, compounds of the invention are useful in the prevention and treatment of prostrate cancer. Furthermore, it has been discovered that compounds of the invention are useful in the prevention and treatment of androgen-independent cancers such as androgen-independent prostrate cancer. Finally, inventive compounds may be used to treat antiandrogen induced withdrawal syndrome.
1. A method to treat prostate cancer in a subject in need thereof, comprising administering an effective amount of a compound having the structure
wherein
E is —C(O)— or —CR 5 R 6 —;
G is —CR 3 R 4 —;
K is —CR 1 R 2 —;
R 1 is —OR 11 , —C(O)—R 12 , —S(O) 0-2 —R 12 or —C(O)—OR 12 ;
R 2 is —H, lower alkyl or substituted lower alkyl;
R 3 and R 5 independently are —H, —OH or lower alkyl;
R 4 and R 6 independently are —H or substituted lower alkyl;
R 11 is —H, alkyl or substituted alkyl;
R 12 is —H, alkyl or substituted alkyl;
R is —OH or unsubstituted lower alkoxy;
R′ is —F or unsubstituted lower alkyl;
n is 0 or 1; and
n′ is 0 or 1.
2. The method of claim 1 wherein the compound has the structure
wherein R 2 is —H or substituted or unsubstituted C 1-4 alkyl.
3. The method of claim 2 wherein the compound has the structure
4. The method of claim 3 wherein the compound has the structure
5. The method of claim 3 wherein the compound has the structure
6. The method of claim 1 wherein the compound has the structure
7. The method of claim 6 wherein K is —CH(OH)— or —CH(OC(O)CH 3 )—.
8. The method of claim 7 wherein G and E are —CH 2 —.
9. The method of claim 7 wherein G is —CH 2 —.
10. The method of claim 9 wherein E is —CH(OH)— or —C(O)—.
11. The method of claim 7 wherein E is —CH 2 —.
12. The method of claim 11 wherein G is —CH(OH)—.
13. The method of claim 6 wherein K is —CH(OC(O)OCH 3 )—.
14. The method of claim 13 wherein G and E are —CH 2 —.
15. The method of claim 13 wherein G is —CH 2 —.
16. The method of claim 15 wherein E is —CH(OH)— or —C(O)—.