US 4,156,092 AGrant

11-Deoxy-6-hydroxy-PGE.sub.1 Compounds

Issue Date:1979-05-22

•37 Claims

Abstract

The present invention provides 11-deoxy-6-hydroxy-PGE.sub.1 compounds which are useful pharmacological agents. These analogs are useful as prostacyclin-like drugs.

Metadata

Assignee

The Upjohn Company

Inventor

Herman W. Smith

Application Information

Application Number:US 9185275

Filing Date:1978-06-23

Priority Date:1977-07-05

Art Unit:126

Classifications

IPC:

C07C17700

Field of Search:

562560260503121404;408;410;410.5;410.9 R;413;501.17

Patent Drawings

This patent does not have any drawings.

Description

The present invention relates to 11-deoxy-6-hydroxy-PGE.sub.1 compounds, the preparation and use of which are described in U.S. Ser. No. 812,794, filed July 5, 1977, now issued as U.S. Pat. No. 4,131,738 on Dec. 26, 1978 .

The essential material constituting a disclosure of the instant invention is incorporated by reference here from U.S. Pat. No. 4,131,738.

Claims

I claim:

1. A prostacyclin analog of the formula ##STR1## wherein Z.sub.1 is (1) --(CH.sub.2).sub.g --CH.sub.2 --CH.sub.2 --, (2) --(ch.sub.2).sub.g --CH.sub.2 --CF.sub.2 --, or (3) trans--(CH.sub.2).sub.g --CH.dbd.CH--, wherein g is the integer one, 2, or 3; Wherein Y.sub.1 is (1) trans--CH.dbd.CH--, (2) cis--CH.dbd.CH--, (3) --ch.sub.2 ch.sub.2 --, (4) trans--CH.dbd.C(Hal)--, or (5) --C.tbd.C--, wherein Hal is chloro or bromo; Wherein M.sub.1 is ##STR2## wherein R.sub.5 is hydrogen or alkyl with one to 4 carbon atoms, inclusive; Wherein L.sub.1 is ##STR3## 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 R.sub.1 is hydrogen; alkyl of one to 12 carbon atoms, inclusive; cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive; phenyl; phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms; phenyl substituted in the para position by ##STR4## WHEREIN R.sub.25 is methyl, phenyl, acetamidophenyl, benzamidophenyl, or --NH.sub.2 ; R.sub.26 is methyl, phenyl, --NH.sub.2, or methoxy; and R.sub.27 is hydrogen or acetamido, inclusive; or a pharamcologically acceptable cation; Wherein m is the integer one to 5, inclusive.

2. A prostacyclin analog according to claim 1, wherein .about.OH is beta.

3. 11-Deoxy-6.beta.-hydroxy-PGE.sub.1, a prostacyclin analog according to claim 2.

4. A prostacyclin analog according to claim 1, wherein .about.OH is alpha.

5. 11-Deoxy-6.alpha.-hydroxy-PGE.sub.1, a prostacyclin analog according to claim 4.

6. 11-Deoxy-6.alpha.-hydroxy-15-methyl-PGE.sub.1, a prostacyclin analog according to claim 4.

7. 11-Deoxy-6.alpha.-hydroxy-16,16-dimethyl-PGE.sub.1, a prostacyclin analog according to claim 4.

8. 11-Deoxy-6.alpha.-hydroxy-16,16-difluoro-PGE.sub.1, a prostacyclin analog according to claim 4.

9. A prostacyclin analog according to claim 1, wherein .about.OH is a mixture of .alpha.-OH and .beta.-OH.

10. A prostacyclin analog according to claim 9, wherein Y.sub.1 is cis--CH.dbd.CH--.

11. 11-Deoxy-6-hydroxy-cis-13-PGE.sub.1, a prostacyclin analog according to claim 10.

12. A prostacyclin analog according to claim 9, wherein Y.sub.1 is --C.tbd.C--.

13. 11-Deoxy-6-hydroxy-13,14-didehydro-PGE.sub.1, a prostacyclin analog according to claim 12.

14. A prostacyclin analog according to claim 9, wherein Y.sub.1 is trans--CH.dbd.C(Hal)--.

15. 11-Deoxy-6-hydroxy-chloro-PGE.sub.1, a prostacyclin analog according to claim 14.

16. A prostacyclin analog according to claim 9, wherein Y.sub.1 is --CH.sub.2 CH.sub.2 --.

17. 11-Deoxy-6-hydroxy-13,14-dihydro-PGE.sub.1, a prostacyclin analog according to claim 16.

18. A prostacyclin analog according to claim 9, wherein Y.sub.1 is trans--CH.dbd.CH--.

19. A prostacyclin analog according to claim 18, wherein Z.sub.1 is --(CH.sub.2).sub.g --(CH.sub.2 --CF.sub.2 --.

20. 11-Deoxy-2,2-difluoro-6-hydroxy-15-methyl-PGE.sub.1, a prostacyclin analog according to claim 19.

21. A prostacyclin analog according to claim 18, wherein Z.sub.1 is trans--(CH.sub.2).sub.g --CH.dbd.CH--.

22. 11-Deoxy-trans-2,3-didehydro-6-hydroxy-PGE.sub.1, a prostacyclin analog according to claim 21.

23. A prostacyclin analog according to claim 18, wherein Z.sub.1 is --(CH.sub.2).sub.g --CH.sub.2 --CH.sub.2 --.

24. A prostacyclin analog according to claim 23, wherein g is one.

25. A prostacyclin analog according to claim 24, wherein m is 3.

26. A prostacyclin analog according to claim 25, wherein R.sub.5 is methyl.

27. 11-Deoxy-6-hydroxy-15-methyl-PGE.sub.1, a prostacyclin analog according to claim 26.

28. A prostacyclin analog according to claim 25, wherein R.sub.5 is hydrogen.

29. A prostacyclin analog according to claim 28, wherein at least one of R.sub.3 and R.sub.4 is fluoro.

30. 11-Deoxy-6-hydroxy-16,16-difluoro-PGE.sub.1, a prostacyclin analog according to claim 29.

31. A prostacyclin analog according to claim 28, wherein at least one of R.sub.3 and R.sub.4 is methyl.

32. 11-Deoxy-6-hydroxy-16,16-dimethyl-PGE.sub.1, a prostacyclin analog according to claim 31.

33. A prostacyclin analog according to claim 28, wherein R.sub.3 and R.sub.4 are both hydrogen.

34. 11-Deoxy-6-hydroxy-PGE.sub.1, methyl ester, a prostacyclin analog according to claim 33.

35. 11-Deoxy-6-hydroxy-PGE.sub.1, tris(hydroxymethyl)aminomethane salt, a prostacyclin analog according to claim 33.

36. 11-Deoxy-6-hydroxy-PGE.sub.1, benzamidophenyl ester, a prostacyclin analog according to claim 33.

37. 11-Deoxy-6-hydroxy-PGE.sub.1, a prostacyclin analog according to claim 33.

Non-Patent Literature (1)

johnson et al., Prostaglandins, 12, 915, (1976).