Progesterone receptor modulators
View Patent ↗The present invention provides new progesterone receptor modulators which are (cis)-8-fluorodibenzo[b,f]pyrido[1,2-d]oxazepine-1-amine compounds and uses thereof.
1. A (cis)-8-fluorodibenzo[b,f]pyrido[1,2-d]oxazepine-1-amine compound according to Formula I
wherein
R1 is (1-4C)alkyl, optionally substituted with one or more halogen atoms; and
R2 is selected from the group consisting of H, halogen, (1-6C)alkyl, and CN; and
R3, R4, R5 each are independently H or F.
2. A compound according to claim 1 , wherein R2 is H.
3. A compound according to claim 1 , wherein R2 is Cl.
4. A compound according to claim 1 , wherein R2 is CN.
5. A compound according to claim 1 , wherein R3 is H, R4 is H and R5 is H.
6. A compound according to claim 1 , wherein R3 is F and R4 and R5 are H.
7. A compound according to claim 1 , wherein R4 is F and R3 and R5 are H.
8. A compound according to claim 1 , wherein R5 is F and R3 and R4 are H.
9. A compound according to claim 1 , wherein R1 is CF 3 .
10. A compound according to claim 1 , wherein R1 is CH 3 .
11. A compound according to claim 1 , wherein R1 is CF 3 and each one of R2, R3, R4 and R5 is H.
12. A compound according to claim 1 , wherein R1 is CF 3 , R2 is Cl and each one of R3, R4 and R5 is H.
13. A compound according to claim 1 , wherein R1 is CF 3 , each one of R2, R3 and R4 is H, and R5 is F.
14. A compound according to claim 1 , wherein R1 is CF 3 , R2 is Cl, both R3 and R4 are H, and R5 is F.
15. A compound according to claim 1 which is laevorotatory.
16. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier.
17. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 1 to a subject in need thereof.
18. 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.
19. A method of treating a gynaecological disorder selected from the group consisting of endometriosis, dysmenorrhea, dysfunctional uterine bleeding and severe premenstrual syndrome, the method comprising administering a pharmaceutically effective amount of a compound according to claim 1 to a subject in need thereof.
20. A (cis)-8-fluorodibenzo[b,f]pyrido[1,2-d]oxazepine-1-amine compound according to Formula II
wherein R1 is (1-4C)alkyl, optionally substituted with one or more halogen atoms; and
R2 is H; and
R3, R4, R5 each are independently H or F.
21. A method of producing a compound of Formula I
by converting a compound of Formula II by use of CuCN, optionally in the presence of CuI,
wherein R1 is (1-4C)alkyl, optionally substituted with one or more halogen atoms; and
R2 is H; and
R3, R4, R5 each are independently H or F,
into a compound of Formula I.
22. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 11 to a subject in need thereof.
23. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 12 to a subject in need thereof.
24. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 13 to a subject in need thereof.
25. A method of contraception comprising administering a contraceptively effective amount of a compound according to claim 14 to a subject in need thereof.
26. A pharmaceutical composition comprising a compound according to claim 11 and a pharmaceutically acceptable carrier.
27. A pharmaceutical composition comprising a compound according to claim 12 and a pharmaceutically acceptable carrier.
28. A pharmaceutical composition comprising a compound according to claim 13 and a pharmaceutically acceptable carrier.
29. A pharmaceutical composition comprising a compound according to claim 14 and a pharmaceutically acceptable carrier.
30. A compound according to claim 13 which is laevorotatory.