Claims
- 1. A compound of the formula ##STR7## wherein R is hydrogen or lower alkyl, R.sub.1 is methyl, hydrogen, or hydroxy; R.sub.2 is hydrogen, methyl or fluoro; and R.sub.2 ' is hydrogen, fluoro, trifluoromethyl or methyl; with the proviso that when R.sub.2 ' is trifluoromethyl, R.sub.2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
- 2. The compound of claim 1 where R.sub.1 is hydroxy.
- 3. The compound of claim 2 wherein R.sub.2 is methyl.
- 4. The compound of claim 3 wherein said compound is [5Z,9.alpha.,11.alpha.,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxy-16-methyl-prosta-5,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
- 5. The compound of claim 3 wherein said compound is (5Z,7.beta.,9.alpha.,11.alpha.,13E,15R)-7-fluoro-6,9-epoxy-11,15-dihydroxy-16,16-dimethyl-prosta-5,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
- 6. The compound of claim 2 wherein R.sub.2 is fluoro.
- 7. The compound of claim 6 wherein R.sub.2 ' is methyl.
- 8. The compound of claim 6 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16-difluoro-11,15-dihydroxyprosta-5,13-dien-1-oic acid or its pharmaceutically acceptable salts.
- 9. The compound of claim 8 wherein said salt is the sodium salt.
- 10. The compound of claim 6 wherein said compound is a lower alkyl ester of (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16-difluoro-11,15-dihydroxyprosta-5,13-dien-1-oic acid.
- 11. The compound of claim 10 wherein said ester is the methyl ester.
- 12. The compound of claim 6 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16,16-triflfuoro-11,15-di hydroxyprosta-5,13-dienoic acid, its lower alkyl esters or its salts.
- 13. The compound of claim 12 wherein said compound is a sodium salt.
- 14. The compound of claim 12 wherein said compound is a methyl ester.
- 15. The compound of claim 12 wherein said compound is the acid.
- 16. The compound of claim 2 wherein R.sub.2 ' is trifluoromethyl.
- 17. The compound of claim 16 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7-fluoro-16-trifluoromethyl-16-methyl-11,15-dihydroxyprosta-5,13-diene-1-oic acid, its lower alkyl esters or its salt.
- 18. The compound of claim 17 wherein said compound is the acid.
- 19. The compound of claim 17 wherein said compound is the salt.
- 20. The compound of claim 17 wherein said compound is the methyl ester.
- 21. The compound of claim 2 wherein R.sub.2 and R.sub.2 ' are hydrogen.
- 22. The compound of claim 21 wherein said compound is a lower alkyl ester.
- 23. The compound of claim 21 wherein the compound is (5Z,9S,11R,13E,15S)-11,15-dihydroxy-6,9-epoxy-7-fluoro-prosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
- 24. The compound of claim 1 wherein R.sub.1 is hydrogen.
- 25. The compound of claim 24 wherein R.sub.2 and R.sub.2 ' are hydrogen.
- 26. The compound of claim 25 wherein said compound is (5Z,9alpha,13E,15S)-6,9-epoxy-7-fluoro-15-hydroxyprosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
- 27. The compound of claim 24 wherein said compound is (5Z,9.alpha.,13E,15R,16R)-7,16-difluoro-6,9-epoxy-15-hydroxy-prosta-5,13-dien-1-oic acid methyl ester.
- 28. The compound of claim 24 wherein said compound is the sodium salt of (5Z,9.alpha.,13E,15R,16R)-7,16-difluoro-15-hydroxy-6,9-epoxy-prosta-5,13-dien-1-oic acid.
- 29. The compound of claim 24 wherein R.sub.2 is methyl.
- 30. The compound of claim 29 wherein said compound is (5Z,9alpha,13E,15R)-6,9-epoxy-7-fluoro-16,16-dimethyl-15-hydroxyprosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
- 31. The compound of claim 29 wherein R.sub.2 is trifluoromethyl.
- 32. The compound of claim 1 wherein R.sub.1 is methyl.
- 33. The compound of claim 32 wherein R.sub.2 is hydrogen.
- 34. The compound of claim 33 wherein R.sub.2 ' is hydrogen.
- 35. The compound of claim 33 wherein R.sub.2 ' is fluoro.
- 36. The compound of claim 32 wherein R.sub.2 is methyl.
- 37. The compound of claim 36 wherein R.sub.2 ' is trifluoromethyl.
- 38. The compound of claim 36 wherein R.sub.2 ' is fluoro.
- 39. The compound of claim 36 wherein R.sub.2 ' is methyl.
- 40. The compound of claim 32 wherein R.sub.2 is fluoro.
- 41. The compound of claim 40 wherein R.sub.2 ' is hydrogen.
- 42. A compound of the formula: ##STR8## wherein R is hydrogen or lower alkyl, R.sub.1 is methyl, hydrogen, or hydroxy; R.sub.2 is hydrogen, methyl or fluoro; and R.sub.2 ' is hydrogen, fluoro, trifluoromethyl or methyl; and with the proviso that when R.sub.2 ' is trifluoromethyl, R.sub.2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
- 43. The compound of claim 42 where R is hydroxy.
- 44. The compound of claim 43 wherein said compound is [4E,6.alpha.,9.alpha.,11.alpha.,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxy-16-dimethyl-prosta-4,13-dien-1-oic acid, its pharmaceutically acceptable salts, or its lower alkyl esters.
- 45. The compound of claim 43 wherein said compound is [4E,6.alpha.,7.beta.,9.alpha.,11.alpha.,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxyprost-4,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
- 46. The compound of claim 42 wherein R.sub.1 is hydrogen.
- 47. The compound of claim 46 wherein said compound is (4E,9.alpha.,13E,15R,16R)-7,16-difluoro-6,9-epoxy-15-hydroxy-prosta-4,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
- 48. The compound of the formula: ##STR9## wherein R.sub.6 is lower alkyl; R.sub.1 ' is hydrogen, methyl or --OR.sub.5, R.sub.2 is methyl, hydrogen or fluoro; R.sub.2 ' is fluoro, hydrogen, trifluoromethyl or methyl; and X is halogen; --OR.sub.5 is hydroxy or forms an acid hydrolyzable ether protecting group with the proviso that when R.sub.2 ' is trifluoromethyl; R.sub.2 is hydrogen or methyl; or their optical antipodes or racemates.
- 49. The compound of claim 48 wherein R.sub.1 ' is --OR.sub.5.
- 50. The compound of claim 49 wherein said compound is (7.beta.,9.alpha.,11.alpha.,13E,15R)-16,16-dimethyl-11,15-di[(tetrahydro-2H-pyran-2-yl)oxy]-6,9-epoxy-7-fluoro-5-iodo-prosta-13-en-1-oic acid methyl ester.
- 51. The compound of claim 49 wherein said compound is (7.beta.,9.alpha.,11.alpha.,13E,15R)-16,16-dimethyl-11,15-dihydroxy-6,9-epoxy-7-fluoro-5-iodo-prosta-13-en-1-oic acid methyl ester.
- 52. The compound of claim 48 wherein R.sub.1 ' is hydrogen.
- 53. The compound of claim 52 wherein said compound is (9.alpha.,13E,15R,16R)-7,16-difluoro-15-hydroxy-6,9-epoxy-5-iodo-prosta-13-en-1-oic acid methyl ester.
- 54. A compound of the formula ##STR10## wherein R is hydrogen or lower alkyl; R.sub.2 is hydrogen or methyl and R.sub.2 ' is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes and racemates.
- 55. A compound of the formula ##STR11## wherein R.sub.6 is lower alkyl; R.sub.2 is methyl or hydrogen; R.sub.2 ' is hydrogen or methyl; X is halogen; OR.sub.5 is hydroxy or forms an acid hydrolyzable ether protecting group or their optical antipodes or racemates.
CROSS REFERENCE TO RELATION APPLICATION
This application is a continuation-in-part application of Ser. No. 337,791, filed Jan. 7, 1982, by Holland, Maag and Rosen and now abandoned, which in turn is a continuation-in-part application of Ser. No. 242,818 filed Mar. 11, 1982, by Holland, Maag and Rosen and now abandoned.
Foreign Referenced Citations (4)
Number |
Date |
Country |
0054795 |
Jun 1982 |
EPX |
0172543 |
Dec 1980 |
JPX |
WO8001002 |
Apr 1981 |
WOX |
2088856 |
Jun 1982 |
GBX |
Non-Patent Literature Citations (3)
Entry |
Fried et al., J. Med. Chem., 1980, 23, pp. 234-237. |
Sukenick, J. Am. Chem. Soc., 1976, 98, pp. 6613-6623. |
Corey et al., J. Am. Chem. Soc., 1977, 99, pp. 2006-2007. |
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
337791 |
Jan 1982 |
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Parent |
242818 |
Mar 1981 |
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