TREA

2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-13,14-didehydro-PGA, PGD, and PGE compounds

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Information

  • Patent Grant
  • 4207422
  • Patent Number
    4,207,422
  • Date Filed
    Friday, February 24, 1978
    46 years ago
  • Date Issued
    Tuesday, June 10, 1980
    44 years ago
Information
Abstract
This invention comprises certain analogs of the prostaglandins in which the C-1 carboxyl 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 prostaglancin analog according to claim 1, wherein D is ##STR6##
  • 3. A prostaglandin analog according to claim 2, wherein R.sub.8 is hydrogen.
  • 4. A prostaglandin analog according to claim 2, wherein R.sub.8 is hydroxy.
  • 5. A prostaglandin analog according to claim 1, wherein D is ##STR7##
  • 6. A prostaglandin analog according to claim 1, wherein D is ##STR8##
  • 7. A prostaglandin analog according to claim 1, wherein D is ##STR9##
  • 8. A prostaglandin analog according to claim 7, wherein M.sub.1 is ##STR10##
  • 9. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 8.
  • 10. A prostaglandin analog according to claim 7, wherein M.sub.1 is ##STR11##
  • 11. A prostaglandin analog according to claim 10, wherein m is 3.
  • 12. A prostaglandin analog according to claim 11, wherein g is 3.
  • 13. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 12.
  • 14. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 12.
  • 15. A prostaglandin analog according to claim 11, wherein g is 1.
  • 16. A prostaglandin analog according to claim 15, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 17. A prostaglandin analog according to claim 16, wherein R.sub.3 and R.sub.4 are both methyl.
  • 18. 2-Decarboxy-2-hydroxymethyl-16,16-dimethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 17.
  • 19. A prostaglandin analog according to claim 15, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 20. A prostaglandin analog according to claim 19, wherein R.sub.3 and R.sub.4 are both fluoro.
  • 21. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 20.
  • 22. A prostaglandin analog according to claim 15, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 23. A prostaglandin analog according to claim 22, wherein R.sub.5 is methyl.
  • 24. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 23.
  • 25. A prostaglandin analog according to claim 22, wherein R.sub.5 is hydrogen.
  • 26. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-11-deoxy-PGE.sub.1, a prostaglandin analog according to claim 25.
  • 27. A prostaglandin analog according to claim 1, wherein D is ##STR12##
  • 28. A prostaglandin analog according to claim 27, wherein M.sub.1 is ##STR13##
  • 29. A prostaglandin analog according to claim 28, wherein m is 3.
  • 30. A prostaglandin analog according to claim 29, wherein g is 3.
  • 31. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 30.
  • 32. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 30.
  • 33. A prostaglandin analog according to claim 29, wherein g is 1.
  • 34. A prostaglandin analog according to claim 33, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 35. 2-Decarboxy-2-hydroxymethyl-15-epi-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 34.
  • 36. A prostaglandin analog according to claim 33, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 37. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-16,16-difluoro-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 36.
  • 38. A prostaglandin analog according to claim 33, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 39. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-epi-15-methyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 38.
  • 40. A prostaglandin analog according to claim 27, wherein M.sub.1 is ##STR14##
  • 41. A prostaglandin analog according to claim 40, wherein m is 3.
  • 42. A prostaglandin analog according to claim 41, wherein g is 3.
  • 43. A prostaglandin analog according to claim 42, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 44. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 43.
  • 45. A prostaglandin analog according to claim 42, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 46. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenylene-4,5,6-trinor-16,16-difluoro-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 45.
  • 47. A prostaglandin analog according to claim 42, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 48. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-3,7-inter-m-phenulene-4,5,6-trinor-15-methyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 47.
  • 49. A prostaglandin analog according to claim 41, wherein g is 1.
  • 50. A prostaglandin analog according to claim 49, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 51. A prostaglandin analog according to claim 50, wherein only one or R.sub.3 and R.sub.4 is methyl.
  • 52. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-16-methyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 51.
  • 53. A prostaglandin analog according to claim 50, wherin R.sub.3 and R.sub.4 are both methyl.
  • 54. 2-Decarboxy-2-hydroxymethyl3,7-inter-m-phenylene-4,5,6-trinor-16,16-dimethyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 53.
  • 55. A prostaglandin analog according to claim 49, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 56. A prostaglandin analog according to claim 55, wherein R.sub.3 and R.sub.4 are both fluoro.
  • 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-16,16-difluoro-13,14-didehydro-PGE.sub.1, 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-16,16-difluoro-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 59.
  • 61. A prostaglandin analog according to claim 49, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 62. A prostaglandin analog according to claim 61, wherein R.sub.5 is methyl.
  • 63. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-15-methyl-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 62.
  • 64. A prostaglandin analog according to claim 61, wherein R.sub.5 is hydrogen.
  • 65. 2-Decarboxy-2-hydroxymethyl-3,7-inter-m-phenylene-4,5,6-trinor-13,14-didehydro-PGE.sub.1, a prostaglandin analog according to claim 64.
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
3935254 Gandolfi et al. Jan 1976
Divisions (2)
Number Date Country
Parent 814500 Jul 1977
Parent 708752 Jul 1976