Progesterone receptor antagonists
View Patent ↗The present invention relates to progesterone receptor antagonists of general formula I: in which R1 can be a hydrogen atom and R2 a hydroxyl group or R1 and R2 together can be an oxo group.
1. A progesterone receptor antagonist of formula I:
in which R1 is a hydrogen atom and R2 a hydroxyl group or R1 and R2 together are an oxo group.
2. 11β-[4-(1,2-Dihydroxyethyl)phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
3. 11 β-[4-[(1R)-1,2-Dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
4. 11β-[4-[(1S)-1,2-Dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
5. 20,20,21,21,21-Pentafluoro-17-hydroxy-11β-[4-(hydroxyacetyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one.
6. The compound of claim 1 , in isolated form.
7. The compound of claim 3 , free of 11β-[4-[(1S)-1,2-Dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
8. The compound of claim 4 , free of 11β-[4-[(1R)-1,2-Dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
9. A pharmaceutical composition comprising a progesterone receptor antagonist as claimed in claim 1 , and a pharmaceutically acceptable carrier.
10. The composition as claimed in claim 9 comprising 11β-[4-(1,2-dihydroxyethyl)phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
11. The composition as claimed in claim 10 comprising 11β-[4-[(1R)-1,2-dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
12. The composition as claimed in claim 10 comprising 11β-[4-[(1S)-1,2-dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
13. The composition as claimed in claim 6 comprising 20,20,21,21,21-pentafluoro-17-hydroxy-11β-[4-(hydroxyacetyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one.
14. A pharmaceutical composition of claim 9 , adapted for oral administration.
15. A pharmaceutical composition of claim 9 , which contains from 0.01 mg to 100 mg of the antagonist.
16. A method for the treatment of endometriosis, myoma or hormone-dependent tumors, comprising administering to a host in need thereof an effective amount of a progesterone receptor antagonist of claim 1 .
17. A method according to claim 16 , wherein the antagonist is 11β-[4-(1,2-dihydroxyethyl)phenyl]-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one.
18. A method according to claim 17 , wherein the antagonist is containing 11β-[4-[(1R)-1,2-dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
19. A method according to claim 17 , wherein the antagonist is 11 β-[4-[(1S)-1,2-dihydroxyethyl]phenyl]-20,20,21,21,21-pentafluoro-17-hydroxy-19-nor-17α-pregna-4,9-dien-3-one.
20. A method according to claim 16 , wherein the antagonist is 20,20,21,21,21-pentafluoro-17-hydroxy-11β-[4-(hydroxyacetyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one.
21. A method for the treatment of endometriosis or carcinoma of the breast, comprising administering to a host in need thereof an effective amount of an antagonist of claim 1 .
22. A method for the treatment of myoma, comprising administering to a host in need thereof an effective amount of an antagonist of claim 1 .
23. A process for the preparation of an antagonist of claim 1 , comprising employing as an intermediate 11β-(4-Ethenylphenyl)-20,20,21,21,21-pentafluoro-5,17-dihydroxy-19-nor-5α,17α-pregn-9-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.
24. A process for the preparation of an antagonist of claim 1 , comprising employing as an intermediate 11β-[4-(1,2-Dihydroxyethyl)phenyl]-20,20,21,21,21-pentafluoro-5,17-dihydroxy-19-nor-5α,17α-pregn-9-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.
25. A process for the preparation of an antagonist of claim 1 , comprising employing as an intermediate 20,20,21,21,21-Pentafluoro-17-hydroxy-5,10α-epoxy-19-nor-5α,17α-pregn-9(11)-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.
26. A process for the preparation of an antagonist of claim 1 , comprising employing as an intermediate 11β-{4-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]phenyl}-20,20,21,21,21-pentafluoro-5,17-dihydroxy-19-nor-5α,17α-pregn-9-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.
27. A process for the preparation of progesterone receptor antagonist 20,20,21,21,21-Pentafluoro-17-hydroxy-11i-[4-(hydroxyacetyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one comprising employing as an intermediate 11β-[4-[2-[[[(1,1-Dimethylethyl)dimethylsilyl]oxy]methyl]-1,3-dioxolan-2-yl]phenyl]-20,20,21,21,21-pentafluoro-5,17-dihydroxy-19-nor-5α,17α-pregn-9-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.
28. A process for the preparation of progesterone receptor antagonist 20,20,21,21,21-Pentafluoro-17-hydroxy-11i-[4-(hydroxyacetyl)phenyl]-19-nor-17α-pregna-4,9-dien-3-one comprising employing as an intermediate 20,20,21,21,21-Pentafluoro-5,17-dihydroxy-11β-[4-[2-(hydroxymethyl)-1,3-dioxolan-2-yl]phenyl]-19-nor-5α,17α-pregn-9-en-3-one 2,2-dimethylpropane-1,3-diyl ketal.