Hydroxylated 15-deoxy derivatives of 9-hydroxy-13-trans-prostenoic acid

• US 3,950,406 A
• Filed: 06/19/1974
• Issued: 04/13/1976
• Est. Priority Date: 07/24/1972
• Status: Expired due to Term

• Current Assignee: American Colloid Company (Minerals Technologies Incorporated)
• Original Assignee: American Colloid Company (Minerals Technologies Incorporated)
• Inventors: Floyd, Middleton Brawner Jr., McGahren, William James, Schaub, Robert Eugene, Weiss, Martin Joseph
• Primary Examiner(s): Gerstl, Robert
• Application Number:
  US05/480,989
• Time in Patent Office: 664 Days
• Field of Search: 260/468 D, 260/514 D
• US Class Current: 562/503
• CPC Class Codes: C07C 405/00 Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
• CPC Class Codes: C07C 405/0016 containing only hydroxy, etherified or esterified hydroxy groups
• CPC Class Codes: C07C 405/0033 containing sulfur
• CPC Class Codes: C07F 1/00 Compounds containing elements of Groups 1 or 11 of the Periodic Table
• CPC Class Codes: C07F 5/062 Al linked exclusively to C
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C07F 9/54 Quaternary phosphonium compounds
• CPC Class Codes: C12P 31/00 Preparation of compounds containing a five-membered ring having two side-chains in ortho position to each other, and having at least one oxygen atom directly bound to the ring in ortho position to one of the side-chains, one side-chain containing, not directly bound to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having at least one oxygen atom bound in gamma-position to the ring, e.g. prostaglandins

Abstract

This disclosure describes certain 15-deoxy prostanoic acid derivatives having a hydroxy group further along in the beta-chain, useful as bronchodilators, hypotensive agents, anti-ulcer agents, or as intermediates.

Claims

1. An optically active compound of the formula:

##SPC28##

or a racemic compound of that formula and the mirror image thereof wherein R₁ is selected from the group consisting of hydroxy, lower alkoxy, tetrahydropyranyloxy, lower alkanoyloxy, ω

-hydroxy substituted lower alkoxy and ω

-tetrahydropyranyloxy substituted lower alkoxy;

R₂ is a moiety selected from the group consisting of those of the formulae;

##EQU23## wherein R'"'"' is selected from the group consisting of a straight chain alkyl group having from 2 to 10 carbon atoms and a straight chain alkyl group having from 2 to 6 carbon atoms and having one branched alkyl group of from 1 to 3 carbon atoms, and R" is selected from the group consisting of a straight chain alkyl group having from 2 to 10 carbon atoms and substituted with an hydroxy group, a straight chain alkyl group having from 2 to 6 carbon atoms and having one branched alkyl group of from 1 to 3 carbon atoms and substituted with an hydroxy group, a straight chain alkenyl group having from 2 to 10 carbon atoms and substituted with an hydroxy group and a straight chain alkenyl group having from 2 to 6 carbon atoms and having one branched alkyl group of from 1 to 3 carbon atoms and substituted with an hydroxy group;

R₃ is selected from the group consisting of hydroxy, alkoxy having from 1 to 12 carbon atoms and tetrahydropyranyloxy; and

Z is a divalent radical selected from the group consisting of those of the formulae;

##EQU24## wherein n is an integer from 3 to 8, inclusive, R₄ is an alkyl group having up to 3 carbon atoms, and R₅ is selected from the group consisting of an alkyl group having up to 3 carbon atoms, a fluorine atom and a phenyl group; and

the pharmacologically acceptable cationic salts thereof when R₃ is hydroxy.

2. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU25## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,20-dihydroxy-13-trans-prostenoic acid.

3. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU26## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,20-dihydroxy-13-trans-prostenoic acid.

4. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU27## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(S)-di-hydroxy-13-trans-prostenoic acid.

5. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU28## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-dihydroxy-13-trans-prostenoic acid.

6. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU29## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

,16-dihydroxy-13-trans-prostenoic acid.

7. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU30## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(R)-di-hydroxy-13-trans-prostenoic acid.

8. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU31## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-epidihydroxy-13-trans-prostenoic acid.

9. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU32## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(S)-dihydroxy-20-methyl-13-trans-prostenoic acid.

10. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU33## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-dihydroxy-20-methyl-13-trans-prostenoic acid.

11. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU34## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

,16-dihydroxy-20-methyl-13-trans-prostenoic acid.

12. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU35## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(R)-dihydroxy-20-methyl-13-trans-prostenoic acid.

13. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU36## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-epi-dihydroxy-20-methyl-13-trans-prostenoic acid.

14. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU37## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(S)-dihydroxy-20-ethyl-13-trans-prostenoic acid.

15. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU38## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-dihydroxy-20-ethyl-13-trans-prostenoic acid.

16. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU39## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

,16-dihydroxy-20-ethyl-13-trans-prostenoic acid.

17. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU40## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(R)-dihydroxy-20-ethyl-13-trans-prostenoic acid.

18. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU41## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-epidihydroxy-20-ethyl-13-trans-prostenoic acid.

19. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU42## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(S)-dihydroxy-20-methyl-13-trans,17-trans-prostadienoic acid.

20. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU43## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16(S)-dihydroxy-20-methyl-13-trans,17-trans-prostadienoic acid.

21. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU44## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

,16-dihydroxy-20-methyl-13-trans,17-trans-prostadienoic acid.

22. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU45## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,16(R)-dihydroxy-20-methyl-13-trans,17-trans-prostadienoic acid.

23. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU46## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,16-epi-dihydroxy-20-methyl-13-trans,17-trans-prostadienoic acid.

24. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU47## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,17(S)-dihydroxy-13-trans-prostenoic acid.

25. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU48## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,17-dihydroxy-13-trans-prostenoic acid.

26. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU49## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

,17(R)-dihydroxy-13-trans-prostenoic acid.

27. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU50## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

,17-epi-dihydroxy-13-trans-prostenoic acid.

28. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU51## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

,17-dihydroxy-13-trans-prostenoic acid.

29. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU52## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

-hydroxy-15(S)-hydroxymethyl-13-trans-prostenoic acid.

30. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU53## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

-hydroxy-15-hydroxymethyl-13-trans-prostenoic acid.

31. The mixture of the two racemic compounds according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU54## R₃ is hydroxy, and Z is --(CH₂)₆ --;

9-oxo-11α

-hydroxy-15-hydroxymethyl-13-trans-prostenoic acid.

32. The optically active compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU55## R₃ is hydroxy, and Z is --(CH₂)₆ --;

l-9-oxo-11α

-hydroxy-15(R)-hydroxymethyl-13-trans-prostenoic acid.

33. The racemic compound according to claim 1 wherein R₁ is hydroxy, R₂ is ##EQU56## R₃ is hydroxy, and Z is --(CH₂)₆ --;

dl-9-oxo-11α

-hydroxy-15-epi-hydroxymethyl-13-trans-prostenoic acid.