2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-.omega.-phenyl-PGF.sub.2 compounds

Abstract

This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl is replaced by a primary alcohol. Also provided in this invention, are novel chemical processes useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

Description

Claims

1. A prostaglandin analog of the formula ##STR1## wherein Z.sub.3 is methylene; wherein R.sub.8 is hydrogen or hydroxy;

wherein Y is trans--CH.dbd.CH--;

wherein M.sub.1 is ##STR2## wherein R.sub.5 is hydrogen or methyl; wherein L.sub.1 is ##STR3## or a mixture of ##STR4## wherein R.sub.3 and R.sub.4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R.sub.3 and R.sub.4 is methyl only when the other is hydrogen or methyl;

wherein g is one, 2, or 3; and

wherein s is zero, one, 2, or 3 and T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl.

2. A compound according to claim 1, wherein R.sub.8 is hydrogen.

3. A compound according to claim 2, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.

4. A compound according to claim 3, wherein at least one of R.sub.3 and R.sub.4 is fluoro.

5. A compound according to claim 4, wherein R.sub.3 and R.sub.4 are both fluoro.

6. A compound according to claim 5, wherein R.sub.5 is methyl.

7. 2-Decarboxy-2-hydroxymethyl-15-methyl-16,16-difluoro-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 6.

8. A compound according to claim 5, wherein R.sub.5 is hydrogen.

9. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 8.

10. A compound according to claim 3, wherein at least one of R.sub.3 and R.sub.4 is methyl.

11. A compound according to claim 10, wherein R.sub.3 and R.sub.4 are both methyl.

12. A compound according to claim 11, wherein R.sub.5 is methyl.

13. 2-Decarboxy-2-hydroxymethyl-15,16,16-trimethyl-17-phenyl-3,7-inter-m-phenylene- 4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 12.

14. A compound according to claim 11, wherein R.sub.5 is hydrogen.

15. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 14.

16. A compound according to claim 3, wherein R.sub.3 and R.sub.4 are both hydrogen.

17. A compound according to claim 16, wherein R.sub.5 is methyl.

18. 2-Decarboxy-2-hydroxymethyl-15-methyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 17.

19. A compound according to claim 16, wherein R.sub.5 is hydrogen.

20. 2-Decarboxy-2-hydroxymethyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-11-deoxy-PGF.sub.1 .alpha., a compound according to claim 19.

21. A compound according to claim 1, wherein R.sub.8 is hydroxy.

22. A compound according to claim 21, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.

23. A compound according to claim 22, wherein at least one of R.sub.3 and R.sub.4 is fluoro.

24. A compound according to claim 23, wherein R.sub.3 and R.sub.4 are both fluoro.

25. A compound according to claim 24, wherein R.sub.5 is methyl.

26. 2-Decarboxy-2-hydroxymethyl-15-methyl-16,16-difluoro-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PGF.sub.1 .alpha., a compound according to claim 25.

27. A compound according to claim 21, wherein R.sub.5 is hydrogen.

28. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PFG.sub.1 .alpha., a compound according to claim 27.

29. A compound according to claim 22, wherein at least one of R.sub.3 and R.sub.4 is methyl.

30. A compound according to claim 29, wherein R.sub.3 and R.sub.4 are both methyl.

31. A compound according to claim 30, wherein R.sub.5 is methyl.

32. 2-Decarboxy-2-hydroxymethyl-15,16,16-trimethyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PGF.sub.1 .alpha., a compound according to claim 31.

33. A compound according to claim 30, wherein R.sub.5 is hydrogen.

34. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PGF.sub.1 .alpha., a compound according to claim 33.

35. A compound according to claim 22, wherein R.sub.3 and R.sub.4 are both hydrogen.

36. A compound according to claim 35, wherein R.sub.5 is methyl.

37. 2-Decarboxy-2-hydroxymethyl-15-methyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PGF.sub.1 .alpha., a compound according to claim 36.

38. A compound according to claim 35, wherein R.sub.5 is hydrogen.

39. 2-Decarboxy-2-hydroxymethyl-17-phenyl-3,7-inter-m-phenylene-4,5,6,18,19,20-hexanor-PGF.sub.1 .alpha., a compound according to claim 38.