Benzothiophene estrogen receptor modulators
This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.
1. A compound selected from:
or a pharmaceutically acceptable salt thereof;
wherein
X is
m is 0, 1, or 2;
o is 0, 1, 2, 3, 4, or 5;
Z is selected from —O—, —C(R 3 ) 2 —, —CHR 3 —, —CH 2 —, —CHF—, —CF 2 —, and —S—;
each R 1 is independently selected from C 1 -C 3 alkyl, halogen, and C 1 -C 3 haloalkyl;
R 2 is selected from:
a) 4-6 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;
b) —NH 2 , —NH(C 1 -C 3 alkyl or C 2 -C 3 haloalkyl), and —N((independently)C 1 -C 3 alkyl or C 2 -C 3 haloalkyl) 2 ;
c) monocyclic 7-8 membered heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ; and
d) 6-12 membered bicyclic or bridged heterocycle optionally substituted with one, two, or three groups independently selected from R 4 ;
R 3 is independently selected from —F, —Cl, —Br, —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 ; and
R 4 and R 5 are independently selected from halogen, C 1 -C 3 alkyl, and C 1 -C 3 haloalkyl.
2. The compound of claim 1 , wherein Z is —O—.
3. The compound of claim 1 , wherein o is 3.
4. The compound of claim 1 , wherein o is 0, 1, or 2.
5. The compound of claim 1 , wherein at least one R 1 is —F.
6. The compound of claim 1 , wherein at least one R 1 is methyl.
7. The compound of claim 1 , wherein R 2 is —N(CH 2 CH 3 ) 2 .
8. The compound of claim 1 , wherein R 2 is selected from
9. The compound of claim 1 , wherein R 3 is —F.
10. The compound of claim 1 , wherein R 4 is —F.
11. The compound of claim 1 , wherein R 4 is C 1 -C 3 haloalkyl.
12. The compound of claim 1 , wherein R 5 is halogen.
13. The compound of claim 1 , wherein R 5 is C 1 -C 3 haloalkyl.
14. The compound of claim 1 selected from
or a pharmaceutically acceptable salt thereof.
15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
16. A method of treating a hormone-related cancer that is estrogen mediated comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.
17. The method of claim 16 , wherein the subject is a human.
18. The method of claim 16 , wherein the cancer is breast, endometrial or ovarian cancer.
19. The method of claim 17 , wherein an effective amount of an additional therapeutic agent is administered.