Pyrrole and pyrazole compounds and methods of use thereof
The disclosure relates to anti-cancer compounds derived from nuclear steroid receptor binders, to products containing the same, as well as to methods of their use and preparation.
1. A compound of Formula:
or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein:
Y is CH, or CR 1 ;
Z is CH;
t is 0, 1 or 2;
z is 0, 1, or 2;
each occurrence of R 1 is independently cyano, halo, C 1-6 alkyl, or C 1-6 haloalkyl; or two R 1 join to form an unsubstituted or substituted heteroaryl or unsubstituted or substituted aryl;
R 2 is hydrogen or halo;
each occurrence of R 3 is independently cyano, halo, C 1-6 alkyl, or CF 3 ; and
R 6 is unsubstituted or substituted heteroaryl.
2. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein Y is CR 1 .
3. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein Y is CH.
4. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein t is 1 or 2.
5. The compound of claim 1 , represented by Formula X:
or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof.
6. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein each R 1 is independently cyano, halo, C 1-6 alkyl, or CF 3 .
7. The compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, wherein R 2 is fluoro.
8. A compound selected from:
or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof.
9. A pharmaceutical composition comprising the compund of claim 1 , or a pharmaceutically acceptable salt, stereoisomer, mixture of stereoisomers, or tautomer thereof, and a pharmaceutically acceptable excipient.
10. A method of treating an androgen receptor overexpressing cancer selected from prostate cancer, breast cancer, bladder cancer, or liver cancer, comprising administering an effective amount of the pharmaceutical composition of claim 9 , to an individual in need thereof.
11. The method of claim 10 , wherein the administering comprises oral administration.
12. The method of claim 10 , further comprising administering an additional chemotherapeutic agent.
13. The method of claim 10 , wherein the cancer is hormone refractory prostate cancer.
14. The method of claim 10 , wherein the cancer is a solid tumor.
15. The method of claim 10 , wherein the cancer is prostate, triple negative breast cancer, bladder, or liver cancer.
16. A method of treating an enzalutamide-resistant cancer, comprising administering an effective amount of the pharmaceutical composition of claim 9 , to an individual in need thereof.