Selective estrogen receptor modulators
View Patent ↗The present invention provides, inter alia, triphenylethylene derivatives, such as, 5-{2-[4-(1,2-Diphenyl-but-1-enyl)-phenyl]-vinyl}-1H-tetrazole, as selective estrogen receptor modulators. Also provided are methods for treating estrogen stimulated diseases in mammals including, but not limited to, for example, breast, uterine, ovarian, prostate and colon cancer; osteoporosis; endometriosis; uterine fibroid; Alzheimer's disease; macular degeneration; urinary incontinence; and type II diabetes, as well as, pharmaceutical compositions comprising at least one compound of the present invention.
1. A compound of Formula (I):
or pharmaceutically acceptable salt form thereof,
wherein R 1 is selected from
R 2 is selected from H, C 1-8 alkyl, and halo;
R 3 is selected from H, C 1-8 alkyl, C 2-8 alkylenyl, halo, and CN;
alternatively R 2 and R 3 , together with the atoms to which they are attached, form a six- or seven-membered ring structure where one or more of the atoms forming the ring may be oxygen;
R 4 is selected from H, OH, C 1-8 alkyl, OC 1-8 alkyl, and halo;
R 5 is selected from H, OH, CN, nitro, C 1-8 alkyl, OC 1-8 alkyl, and halo;
R 7 is selected from H and C 1-8 alkyl; and
the bond represented by a broken line and a solid line is an optional double bond.
2. A compound according to claim 1 , wherein R 7 is H.
3. A compound according to claim 1 , wherein R 7 is —CH 3 .
4. A compound according to claim 1 wherein R 2 and R 3 together with the atoms to which they are attached form a seven-membered ring.
5. A compound according to claim 4 , wherein one of the atoms forming the seven-membered ring is an O.
6. A compound according to claim 4 , wherein R 4 is —OCH 3 .
7. A compound according to claim 4 , wherein R 7 is H.
8. A compound according to claim 1 wherein R 2 and R 3 together with the atoms to which they are attached form a six-membered ring.
9. A compound according to claim 8 , wherein one of the atoms forming the six-membered ring is an O.
10. A compound according to claim 1 , wherein R 3 is CH 3 .
11. A compound according to claim 1 , wherein R 3 is CN.
12. A compound according to claim 1 , wherein R 3 is CH═CH 2 .
13. A compound according to claim 1 , wherein R 2 is H.
14. A compound according to claim 1 , wherein R 3 is —CH 2 CH 3 .
15. A compound according to claim 14 , wherein R 7 is —CH 3 .
16. A compound according to claim 1 , wherein R 4 and R 5 are each independently H.
17. A compound according to claim 1 , wherein R 4 is —OCH 3 .
18. A compound according to claim 1 , wherein the bond represented by a broken line and a solid line is a double bond.
19. A compound according to claim 1 , wherein the compound is selected from:
e) 5-{2-[4-(1,2-Diphenyl-but-1-enyl)-phenyl]-vinyl}-1H-tetrazole;
j) 5-{2-[4-(6-Phenyl-8,9-dihydro-7H-benzocyclohepten-5-yl)-phenyl]-vinyl}-1H-tetrazole;
k) 5-{2-[4-(1,2-Diphenyl-but-1-enyl)-phenyl]-vinyl}-1-methyl-1H-tetrazole; and
l) 5-(2-{4-[6-(3-Methoxy-phenyl)-8,9-dihydro-7H-benzocyclohepten-5-yl]-phenyl}-vinyl)-1H-tetrazole.
20. A pharmaceutical composition comprising at least one pharmaceutically acceptable carrier in combination with a therapeutically effective amount of at least one compound of claim 1 .
21. A method of treating breast, uterine, ovarian, prostate or colon cancer; osteoporosis; endometriosis; uterine fibroid; Alzheimer's disease; macular degeneration; urinary incontinence; or type II diabetes, comprising: administering to a host in need of such treatment a therapeutically effective amount of at least one compound of claim 1 .