TREA

2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-13,14-didehydro-PGF compounds

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Information

  • Patent Grant
  • 4211884
  • Patent Number
    4,211,884
  • Date Filed
    Friday, February 24, 1978
    46 years ago
  • Date Issued
    Tuesday, July 8, 1980
    44 years ago
Information
Abstract
This invention comprises certain analogs of the prostaglandins in which the C-1 carboxylic is replaced by a primary alcohol and the double bond between C-13 and C-14 is replaced by a triple bond. 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 D is ##STR2## wherein R.sub.8 is hydrogen or hydroxy; wherein M.sub.1 is ##STR3## wherein R.sub.5 is hydrogen or methyl; wherein L.sub.1 is ##STR4## or a mixture of ##STR5## 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 fluoro only when the other is hydrogen or fluoro;
  • wherein g is one, 2, or 3; and
  • wherein m is one to 5, inclusive.
  • 2. A prostaglandin analog according to claim 1, wherein D is ##STR6##
  • 3. A prostaglandin analog according to claim 2, wherein M.sub.1 is ##STR7##
  • 4. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 3.
  • 5. A prostaglandin analog according to claim 2, wherein M.sub.1 is ##STR8##
  • 6. A prostaglandin analog according to claim 5, wherein m is 3.
  • 7. A prostaglandin analog according to claim 6, wherein g is 3.
  • 8. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 7.
  • 9. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 7.
  • 10. A prostaglandin analog according to claim 6, wherein g is 1.
  • 11. A prostaglandin analog according to claim 10, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 12. A prostaglandin analog according to claim 11, wherein R.sub.3 and R.sub.4 are both methyl.
  • 13. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 12.
  • 14. A prostaglandin analog according to claim 10, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 15. A prostaglandin analog according to claim 14, wherein R.sub.3 and R.sub.4 are both fluoro.
  • 16. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 1.
  • 17. A prostaglandin analog according to claim 10, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 18. A prostaglandin analog according to claim 17, wherein R.sub.5 is methyl.
  • 19. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 18.
  • 20. A prostaglandin analog according to claim 17, wherein R.sub.5 is hydrogen.
  • 21. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 20.
  • 22. A prostaglandin analog according to claim 1, wherein D is ##STR9##
  • 23. A prostaglandin analog according to claim 22, wherein M.sub.1 is ##STR10##
  • 24. A prostaglandin analog according to claim 23, wherein m is 3.
  • 25. A prostaglandin analog according to claim 23, wherein g is 3.
  • 26. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 25.
  • 27. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 25.
  • 28. A prostaglandin analog according to claim 24, wherein g is 1.
  • 29. A prostaglandin analog according to claim 28, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 30. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 29.
  • 31. A prostaglandin analog according to claim 28, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 32. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-16,16-difluoro-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 31.
  • 33. A prostaglandin analog according to claim 28, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 34. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 33.
  • 35. A prostaglandin analog according to claim 22, wherein M.sub.1 is ##STR11##
  • 36. A prostaglandin analog according to claim 35, wherein m is 3.
  • 37. A prostaglandin analog according to claim 36, wherein g is 3.
  • 38. A prostaglandin analog according to claim 37, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 39. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 38.
  • 40. A prostaglandin analog according to claim 37, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 41. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 40.
  • 42. A prostaglandin analog according to claim 37, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 43. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 42.
  • 44. A prostaglandin analog according to claim 36, wherein g is 1.
  • 45. A prostaglandin analog according to claim 44, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 46. A prostaglandin analog according to claim 45, wherein only one of R.sub.3 and R.sub.4 is methyl.
  • 47. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16-methyl-13,14-didehydro-PGF.sub.2 .beta., a prostaglandin analog according to claim 46.
  • 48. A prostaglandin analog according to claim 45, wherein R.sub.3 and R.sub.4 are both methyl.
  • 49. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 48.
  • 50. A prostaglandin analog according to claim 44, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 51. A prostaglandin analog according to claim 50, wherein R.sub.3 and R.sub.4 are both fluoro.
  • 52. A prostaglandin analog according to claim 51, wherein R.sub.5 is methyl.
  • 53. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-16,16-difluoro-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 52.
  • 54. A prostaglandin analog according to claim 51, wherein R.sub.5 is hydrogen.
  • 55. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 54.
  • 56. A prostaglandin analog according to claim 44, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 57. A prostaglandin analog according to claim 56, wherein R.sub.5 is methyl.
  • 58. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 57.
  • 59. A prostaglandin analog according to claim 56, wherein R.sub.5 is hydrogen.
  • 60. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-dihydro-PGF.sub.1 .beta., a prostaglandin analog according to claim 59.
Parent Case Info

The present application is a divisional application of Ser. No. 814,500, filed July 11, 1977, issued as U.S. Pat. No. 4,134,921 on Jan. 16, 1979; which application is a divisional application of Ser. No. 708,752, filed July 26, 1976, issued as U.S. Pat. No. 4,058,564 on Nov. 15, 1977.

US Referenced Citations (1)
Number Name Date Kind
3984400 Eggler et al. Oct 1976
Divisions (2)
Number Date Country
Parent 814500 Jul 1977
Parent 708752 Jul 1976