Progesterone receptor modulators
View Patent ↗The present invention provides new progesterone receptor modulators which are dibenzo[b,f]pyrido[1,2-d]oxazepine-2-amines or dibenzo[b,f]prido[1,2-d]thiazepine-2-amines, and uses thereof.
1. A (cis)-dibenzo[bf]pyrido[1,2-d]oxazepine-2-amine or a (cis)-dibenzo[b,f]pyrido[1,2-d]thiazepine-2-amine according to Formula I
wherein
R1 is selected from the group consisting of (1-5C)acyl, (1-5C)thioacyl, (1-4C)alkylsulfonyl, and (1-4C)alkoxycarbonyl, each optionally substituted with one or more halogen atoms; and
R2 and R3 are each independently selected from the group consisting of H, halogen, cyano, nitro, and thiocarbamyl; and
R4 and R5 are each independently selected from the group consisting of H, (1-4C)alkyl, and (1-4C)alkoxy; and
X is selected from the group consisting of —O—, —S—, —SO—, and —SO 2 —;
provided that, when R2 is C1, R5 is not H or a racemate thereof.
2. The compound according to claim 1 , wherein R1 is COCH 3 .
3. The compound according to claim 1 , wherein R1 is COCF 3 .
4. The compound according to claim 1 wherein R2 is H.
5. The compound according to claim 1 wherein in that R2 is Cl.
6. The compound according to claim 1 wherein R2 is F.
7. The compound according to claim 1 wherein R3 is CN.
8. The compound according to claim 1 wherein R5 is methyl.
9. The compound according to claim 1 wherein R5 is methoxy.
10. The compound according to claim 1 wherein X is O.
11. The compound according to claim 10 wherein R1 is COCF 3 , R2 is H, R3 is CN, R4 is H, and R5 is CH 3 .
12. The compound according to claim 10 wherein R1 is COCF3, R2 is H, R3 is CN, R4 is H and R5 is OCH 3 .
13. The compound according to claim 10 wherein R1 is COCF 3 , R2 is F, R3 is CN, R4 is H, and R5 is CH 3 .
14. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
15. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 1 to a subject in need thereof.
16. A method of hormone replacement therapy comprising administering a pharmaceutically effective amount of a compound according to claim 1 to a subject in need thereof.
17. A method of treating a disorder selected from endometriosis, dysmenorrhea, and dysfunctional uterine bleeding, comprising administering a pharmaceutically effective amount of a compound according to claim 1 to a subject in need thereof.