Progesterone receptor modulators

1. A compound according to Formula I, wherein

X is O, NOH, NO(1-4C)alkyl, NO(1-4C)acyl;

A1-A5 are C, substituted with R1, or N, provided that at least one and not more than three of A1-A5 are N; or

one or two of A1, A2 and A5 are N, and the others are C, substituted with R1, and A3 and A4 together represent a fused benzo ring or a fused five- or six-membered nitrogen-containing aromatic ring, both optionally substituted with one or more halogen and/or (1-4C)alkyl;

each R1 is independently selected from H, halogen, (1-4C)alkyl and (1-4C)alkoxy;

R2 is H, (1-4C)alkyl, or (1-6C) alkenyl, both optionally substituted with an (6-10C)aryl group, which is optionally substituted with one or more halogen and/or (1-4C)alkyl; and

R3 is H or (1-4C)alkyl, optionally substituted with one or more halogen; and

R4 is cyclopropyl or cyclopropenyl both optionally substituted with one or more halogen and/or (1-4C)alkyl; or

R2 together with R3 forms a 3-, 4-, 5- or 6-membered carbocyclic ring; and

R4 is cyclopropyl or cyclopropenyl both optionally substituted with one or more halogen and/or (1-4C)alkyl); or

R2 is H or (1-4C)alkyl; and

R3 together with R4 forms a 5-, 6- or 7-membered saturated or unsaturated carbocyclic ring;

R5 is H or (1-4C)alkyl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein A1-A5 are C, substituted with R1, or N, provided that at least one and not more than three of A1-A5 are N.

3. A compound according to claim l, wherein one or two of A1, A2 and A5 are N, and the others are C, substituted with R1, and A3 and A4 together represent a fused benzo ring or a fused five- or six-membered nitrogen-containing aromatic ring, both optionally substituted with halogen and/or (1-4C)alkyl.

4. A compound according to claim 1 , wherein

R2 is H, (1-4C)alkyl or (1-6C)alkenyl, both optionally substituted with an (6-10C)aryl group, which is optionally substituted with one or more halogen and/or (1-4C)alkyl; and

R3 is H or (1-4C)alkyl, optionally substituted with one or more halogen; and

R4 is cyclopropyl or cyclopropenyl, both optionally substituted with one or more halogen and/or (1-4C)alkyl.

5. A compound according to claim 1 ,

wherein

R2 together with R3 forms a 3-, 4-, 5- or 6-membered carbocyclic ring; and

R4 is cyclopropyl or cyclopropenyl, both optionally substituted with one or more halogen and/or (1-4C)alkyl.

6. A compound according to claim 1 , wherein

R2 is H or (1-4C)alkyl; and

R3 together with R4 forms a 5-, 6- or 7-membered saturated or unsaturated carbocyclic ring.

7. A compound according to claim 2 , wherein

R2 is H, (1-4C)alkyl or (1-6C)alkenyl, both optionally substituted with an (6-10C)aryl group, which is optionally substituted with one or more halogen and/or (1-4C)alkyl; and

R3 is H or (1-4C)alkyl optionally substituted with one or more halogen; and

R4 is cyclopropyl or cyclopropenyl both optionally substituted with one or more halogen and/or (1-4C)alkyl.

8. A compound according to claim 2 ,

wherein

R2 together with R3 forms a 3-, 4-, 5- or 6-membered carbocyclic ring; and

R4 is cyclopropyl or cyclopropenyl, both optionally substituted with one or more halogen and/or (1-4C)alkyl.

9. A compound according to claim 2 , wherein

R2 is H or (1-4C)alkyl; and

R3 together with R4 forms a 5-, 6- or 7-membered saturated or unsaturated carbocyclic ring.

10. A compound according to claim 3 , wherein

R2 is H, (1-4C)alkyl or (1-6C)alkenyl, both optionally substituted with an (6-10C)aryl group which is optionally substituted with one or more halogen and/or (1-4C)alkyl; and

R3 is H or (1-4C)alkyl optionally substituted with one or more halogen; and

R4 is cyclopropyl or cyclopropenyl both optionally substituted with one or more halogen and/or (1-4C)alkyl.

11. A compound according to claim 3 , wherein

R2 together with R3 forms a 3-, 4-, 5- or 6-membered carbocyclic ring; and

R4 is cyclopropyl or cyclopropenyl, both optionally substituted with one or more halogen and/or (1-4C)alkyl.

12. A compound according to claim 3 ,

wherein

R2 is H or (1-4C)alkyl; and

R3 together with R4 forms a 5-, 6- or 7-membered saturated or unsaturated carbocyclic ring.

13. A compound according to claim 1 , wherein X is O.

14. A compound according to claim 4 , wherein R4 is cyclopropyl.

15. A compound according to claim 5 , wherein R4 is cyclopropyl.

16. A compound according to claim 2 , wherein A1, A3, A4 and A5 are C, substituted with R1, and A2 is N.

17. A compound according to claim 13 , wherein

A1, A3, A4 and A5 are C, substituted with R1, and A2 is N;

R2 is H, (1-4C)alkyl or (1-4C)alkenyl; and

R3 is H or (1-4C)alkyl, optionally substituted with one or more halogen; and

R4 is cyclopropyl; or

R2 together with R3 forms a 3-, 4-, 5- or 6-membered carbocyclic ring; and

R4 is cyclopropyl.

18. A compound according to claim 13 , wherein

A1, A3, A4 and A5 are C;

A2 is N;

R1 is H

R2 is ethenyl;

R3 is H;

R4 is cyclopropyl; and

R5 is H.

19. A compound according to claim 4 , wherein R2 is H, (1-4C)alkyl or (1-4C)alkenyl.

20. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

21. A method of contraception comprising administering a pharmaceutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof.

22. 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 or a pharmaceutically acceptable salt thereof to a subject in need thereof.

23. A method of hormone replacement therapy comprising administering a pharmaceutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof.

24. A compound of the formula

25. A pharmaceutical composition comprising a compound according to claim 24 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

26. The method according to claim 22 , wherein the gynaecological disorder is endometriosis.

27. 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 the compound according to claim 24 or a pharmaceutically acceptable salt thereof to a subject in need thereof.

28. The method according to claim 27 , wherein the gynaecological disorder is endometriosis.