TREA

2-Decarboxy-2-hydroxy-methyl-13,14-didehydro-17-phenyl PGF compounds

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Information

  • Patent Grant
  • 4206311
  • Patent Number
    4,206,311
  • Date Filed
    Friday, February 24, 1978
    46 years ago
  • Date Issued
    Tuesday, June 3, 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 or methyl being the same or different;
  • wherein Z.sub.10 is
  • (1) cis--CH.dbd.CH--CH--(CH.sub.2).sub.g --CH.sub.2 --,
  • (2) cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CF.sub.2 --,
  • (3) cis--CH.sub.2 --CH.dbd.CH--(CH.sub.2).sub.g --CH.sub.2 --,
  • (4) --(CH.sub.2).sub.3 --(CH.sub.2).sub.g --CH.sub.2,
  • (5) --(CH.sub.2).sub.3 --(CH.sub.2).sub.g --CF.sub.2 --, or
  • (6) --CH.sub.2 --O--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --,
  • wherein g is one, 2, or 3; and
  • wherein s is one to 3, inclusive 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 are other than alkyl.
  • 2. A prostaglandin 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 5, wherein Z.sub.10 is cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CF.sub.2 --.
  • 7. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 6.
  • 8. A prostaglandin analog according to claim 5, wherein Z.sub.10 is --(CH.sub.2).sub.3 --(CH.sub.2).sub.g --CF.sub.2 --.
  • 9. 2-Decarboxy-2-hydroxymethyl-2,2-difluoro-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 8.
  • 10. A prostaglandin analog according to claim 5, wherein Z.sub.10 is cis--CH.sub.2 CH.dbd.CH--(CH.sub.2l ).sub.g --CH.sub.2 --.
  • 11. 2-Decarboxy-2-hydroxymethyl-cis-4,5-didehydro-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 10.
  • 12. A prostaglandin analog according to claim 5, wherein Z.sub.10 is --CH.sub.2 --O--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --.
  • 13. 2-Decarboxy-2-hydroxymethyl-5-oxa-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 12.
  • 14. A prostaglandin analog according to claim 5, wherein Z.sub.10 is --(CH.sub.2).sub.3 --(CH.sub.2).sub.g --CH.sub.2 --.
  • 15. A prostaglandin analog according to claim 14, wherein M.sub.1 is ##STR8##
  • 16. 2-Decarboxy-2-hydroxymethyl-15-epi-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 15.
  • 17. A prostaglandin analog according to claim 14, wherein M.sub.1 is ##STR9##
  • 18. A prostaglandin analog according to claim 17, wherein m is 3.
  • 19. A prostaglandin analog according to claim 18, wherein g is 3.
  • 20. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-methyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 19.
  • 21. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 19.
  • 22. A prostaglandin analog according to claim 18, wherein g is 1.
  • 23. A prostaglandin analog according to claim 22, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 24. A prostaglandin analog according to claim 23, wherein R.sub.3 and R.sub.4 are both methyl.
  • 25. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 24.
  • 26. A prostaglandin analog according to claim 22, wherein at least two of R.sub.3, R.sub.4, and R.sub.5 are methyl.
  • 27. A prostaglandin analog according to claim 26, wherein R.sub.3, R.sub.4, and R.sub.5 are all methyl.
  • 28. 2-Decarboxy-2-hydroxymethyl-15,16,16-trimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 27.
  • 29. A prostaglandin analog according to claim 22, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 30. A prostaglandin analog according to claim 29, wherein R.sub.5 is methyl.
  • 31. 2-Decarboxy-2-hydroxymethyl-15-methyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 30.
  • 32. A prostaglandin analog according to claim 29, wherein R.sub.5 is hydrogen.
  • 33. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.1 .alpha., a prostaglandin analog according to claim 32.
  • 34. A prostaglandin analog according to claim 5, wherein Z.sub.10 is cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --.
  • 35. A prostaglandin analog according to claim 34, wherein M.sub.1 is ##STR10##
  • 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. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-epi-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 37.
  • 39. A prostaglandin analog according to claim 36, wherein g is 1.
  • 40. A prostaglandin analog according to claim 39, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 41. 2-Decarboxy-2-hydroxymethyl-15-epi-13,14-didehydro-16-methyl-17-phenyl-18,19,20-trinor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 40.
  • 42. A prostaglandin analog according to claim 39, wherein at least two of R.sub.3, R.sub.4, and R.sub.5 are methyl.
  • 43. 2-Decarboxy-2-hydroxymethyl-15-epi-15,16-dimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 42.
  • 44. A prostaglandin analog according to claim 39, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 45. 2-Decarboxy-2-hydroxymethyl-15-epi-15-methyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGE.sub.2 .alpha., a prostaglandin analog according to claim 44.
  • 46. A prostaglandin analog according to claim 34, wherein M.sub.1 is ##STR11##
  • 47. A prostaglandin analog according to claim 46, wherein m is 3.
  • 48. A prostaglandin analog according to claim 47, wherein g is 3.
  • 49. A prostaglandin analog according to claim 48, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 50. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-16,16-dimethyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 49.
  • 51. A prostaglandin analog according to claim 48, wherein at least two of R.sub.3, R.sub.4, and R.sub.5 are methyl.
  • 52. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15,16-dimethyl-13,14-didehydro-17-phenyl-18,19,20-trinor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 51.
  • 53. A prostaglandin analog according to claim 48, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 54. 2-Decarboxy-2-hydroxymethyl-2a,2b-dihomo-15-methyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 53.
  • 55. A prostaglandin analog according to claim 47, wherein g is 1.
  • 56. A prostaglandin analog according to claim 55, wherein at least one of R.sub.3 and R.sub.4 is methyl.
  • 57. A prostaglandin analog according to claim 56, wherein only one of R.sub.3 and R.sub.4 is methyl.
  • 58. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16-methyl-17-phenyl-18,19,20-trinor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 57.
  • 59. A prostaglandin analog according to claim 56, wherein R.sub.3 and R.sub.4 are both methyl.
  • 60. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-16,16-dimethyl-17-phenyl-18,19,20-trinor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 59.
  • 61. A prostaglandin analog according to claim 55, wherein at least one of R.sub.3 and R.sub.4 is fluoro.
  • 62. A prostaglandin analog according to claim 61, wherein R.sub.2 and R.sub.4 are both fluoro.
  • 63. A prostaglandin analog according to claim 62, wherein R.sub.5 is methyl.
  • 64. 2-Decarboxy-2-hydroxymethyl-15-methyl-16,16-difluoro-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 63.
  • 65. A prostaglandin analog according to claim 62, wherein R.sub.5 is hydrogen.
  • 66. 2-Decarboxy-2-hydroxymethyl-16,16-difluoro-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 65.
  • 67. A prostaglandin analog according to claim 55, wherein R.sub.3 and R.sub.4 are both hydrogen.
  • 68. A prostaglandin analog according to claim 67, wherein R.sub.5 is methyl.
  • 69. 2-Decarboxy-2-hydroxymethyl-15-methyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 68.
  • 70. A prostaglandin analog according to claim 67, wherein R.sub.5 is hydrogen.
  • 71. 2-Decarboxy-2-hydroxymethyl-13,14-didehydro-17-phenyl-17,18,19,20-tetranor-PGF.sub.2 .alpha., a prostaglandin analog according to claim 70.
Parent Case Info

The present application is a divisional application of Ser. No. 814,410, filed July 11, 1977, now U.S. Pat. No. 4,137,270, 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
3932496 Jung Jan 1976
Divisions (2)
Number Date Country
Parent 814410 Jul 1977
Parent 708752 Jul 1976