Claims
- 1. A 3,20-dioxo-7-halogeno-1,4-pregnadiene of the following formula: ##STR10## wherein A is hydrogen, and provided Y is (H,.beta.OH), chlorine, fluorine or methyl;
- B is hydrogen or, together with Q, is a 14.alpha.,17.alpha.-alkylideneoxy derivative;
- X is a member selected from the group consisting of hydrogen having an atomic weight less than 100;
- Y is a member selected from the group consisting of (H,H) provided X is hydrogen, oxygen, (H,.beta.OH), (H,.beta.OCOH); and (H,.beta.-halogen) provided X is chlorine or bromine, said .beta.-halogen having an atomic weight of less than 100 and being at least as electronegative as X;
- Z is fluorine, chlorine, bromine and iodine;
- Q is a member selected from the group consisting of hydrogen provided W is a member selected from the group consisting of (H,H) and (H, lower akyl); chlorine; bromine; and OV wherein V is a member selected from the group consisting of hydrogen and an acyl radical of a hydrocarboncarboxylic acid having up to 12 carbon atoms or of benzoic acid substituted by a halogen or methoxy group;
- W is a member selected from the group consisting of (H,H); (H, lower alkyl); (H,.alpha.-OV.sub.1) wherein V.sub.1 is a member selected from the group consisting of hydrogen and an acyl radical of an acid selected from the group consisting of a hydrocarbonacarboxylic acid having up to 12 carbon atoms, benzoic acid substituted by a halogen or methoxy group, retinoic acid, and isonicotinic acid; .dbd.CHT wherein T is a member selected from the group consisting of hydrogen, lower alkyl, fluorine and chlorine, and
- W and Q taken together is a member selected from the group consisting of 16.alpha.,17.alpha.-lower alkylidenedioxy; 16.alpha.,17.alpha.-cycloalkylidenedioxy; the grouping ##STR11## wherein R is lower alkyl; and the grouping ##STR12## wherein R.sub.1 is lower alkyl or phenyl; M is a member selected from the group consisting of --OR.sub.2 when Q is O-acyl, R.sub.2 being lower alkyl or halogeno lower alkyl; --CHO, acetals, hemiacetals and acylals thereof; --COOR.sub.3 wherein R.sub.3 is an alkyl having up to 12 carbon atoms; --CH.sub.2 G wherein G is a member selected from the group consisting of hydrogen, halogen having an atomic weight of less than 100, OV.sub.2 wherein V.sub.2 is a member selected from the group consisting of hydrogen and an acyl radical of an acid selected from the group consisting of a hydrocarboncarboxylic acid having up to 12 carbon atoms, benzoic acid substituted by a halogen or methoxy group, retinoic acid, isonicotinic acid, phosphoric acid and mono- and dialkali, and alkaline earth metals salts thereof; and OV.sub.2 together with OV is a member selected from the group consisting of alkylidene dioxy and alkylorthoalkanoate;
- when W is hydrogen, the D-homo analogs thereof.
- 2. A compound of claim 1 wherein Z is chlorine or bromine.
- 3. A compound of claim 2 wherein X is hydrogen and Y is (H,.beta.OH).
- 4. A 7.alpha.-Z compound of claim 1 wherein M is CH.sub.2 OV.sub.2, Q is OV and A and B are hydrogen.
- 5. A compound of claim 4 wherein X is hydrogen, Y is (H,.beta.OH), W is (H,CH.sub.3) or .dbd.CH.sub.2, and Z is chloro or bromo, said compound having the following formula: ##STR13## wherein Z' is chlorine or bromine; W' is (H,CH.sub.3) or .dbd.CH.sub.2 ;
- V and V.sub.2 are each hydrogen or an acyl radical of a hydrocarboncarboxylic acid having up to 12 carbon atoms.
- 6. A compound of claim 5 wherein V and V.sub.2 are acyl radicals of hydrocarboncarboxylic acids having up to 8 carbon atoms.
- 7. A compound of claim 6 wherein V is propionyl.
- 8. A compound of claim 6 wherein V is n-butyryl.
- 9. A compound of claim 6 wherein V is benzoyl.
- 10. A compound of claim 5 wherein W is (H,.alpha.--CH.sub.3) and V and V.sub.2 are acid residues of hydrocarboncarboxylic acids having up to 8 carbon atoms.
- 11. A compound of claim 10 wherein V is propionyl.
- 12. A compound of claim 10 wherein V and V.sub.2 are each propionyl and Z' is chlorine, said compound being 7.alpha.-chloro-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dipropionate.
- 13. A compound of claim 10 wherein V and V.sub.2 are each propionyl and Z' is bromine, said compound being 7.alpha.-bromo-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dipropionate.
- 14. A compound of claim 10 wherein V is benzoyl.
- 15. A compound of claim 10 wherein V is benzoyl, V.sub.2 is acetyl and Z' is bromine, said compound being 7.alpha.-bromo-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17-benzoate 21-acetate.
- 16. A compound of claim 5 wherein W is .dbd.CH.sub.2, V and V.sub.2 are each propionyl and Z' is chlorine, said compound being 7.alpha.-chloro-16-methylene-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dipropionate.
- 17. A compound of claim 1 wherein X, Y and Z are chlorine, W is (H,.alpha.-CH.sub.3), V and V.sub.2 are propionyl, said compound being 7.alpha.,9.alpha.,11.beta.-trichloro-16.alpha.-methyl-1,4-pregnadiene-17.alpha.,21-diol-3,20-dione 17,21-dipropionate.
- 18. A compound of claim 4 wherein X is hydrogen, Y is oxygen, and W is (H,CH.sub.3) or .dbd.CH.sub.2, said compound having the following formula: ##STR14## wherein Z' is chlorine or bromine; W' is (H,CH.sub.3) or .dbd.CH.sub.2 ;
- V and V.sub.2 are each hydrogen or an acyl radical of a hydrocarboncarboxylic acid having up to 12 carbon atoms.
- 19. A pharmaceutical composition for use in the treatment of inflammation, which comprises an effective amount of a 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadiene of claim 1 together with a non-toxic, pharmaceutically acceptable carrier.
- 20. A pharmaceutical composition of claim 19 for use in the topical treatment of inflammation, which comprises an effective amount of a 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadiene of claim 5,
- together with a non-toxic, pharmaceutically acceptable carrier.
- 21. A pharmaceutical composition of claim 20 comprising an effective amount of 7.alpha.-Z'-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17-propionate 21-lower alkanoate, Z' being chlorine or bromine, together with a non-toxic, pharmaceutically acceptable carrier.
- 22. A pharmaceutical composition of claim 20 comprising an effective amount of 7.alpha.-Z'-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17-benzoate 21-lower alkanoate, Z' being chlorine or bromine, together with a non-toxic, pharmaceutically acceptable carrier.
- 23. The method of treating an inflammatory condition in a warm-blooded animal responsive to treatment with anti-inflammatory agents which comprises administering to said animal a non-toxic, anti-inflammatory effective amount of a 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadiene of claim 1 together with a non-toxic, pharmaceutically acceptable carrier.
- 24. The method according to claim 23 for the treatment of a topical inflammatory condition which comprises applying to the inflamed area in a concentration effective for the topical treatment of inflammation, a 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadiene of claim 5, together with a non-toxic, pharmaceutically acceptable carrier.
- 25. The method of claim 24 wherein said 7.alpha.-halogeno-3,20-dioxo-1,4-pregnadiene is 7.alpha.-chloro-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dipropionate.
- 26. The method according to claim 24 wherein said 7.alpha.-halogeno-3,20-dioxo-1,4-pregnadiene is 7.alpha.-bromo-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17-benzoate 21-acetate.
- 27. The method according to claim 24 wherein said 7.alpha.-halogeno-3,20-dioxo-1,4-pregnadiene is 7.alpha.-bromo-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dipropionate.
- 28. A compound of claim 1 wherein A, B and X are hydrogen, Y is (H,.beta.OH); W is (H,.alpha.--CH.sub.3); Q is benzoyloxy; M is --CH.sub.2 OCOCH.sub.3, and Z is fluorine, said compound being 7.alpha.-fluoro-16.alpha.-methyl-1,4-pregnadiene-11.beta.,17.alpha.,21-triol-3,20-dione 17-benzoate 21-acetate.
- 29. A compound of claim 1 wherein A, B and X are hydrogen; Y is (H,.beta.OH); Q and W together are isopropylidenedioxy; M is --CH.sub.2 OCOCH.sub.3, and Z is bromine, said compound being 7.alpha.-bromo-16.alpha.,17.alpha.-isopropylidenedioxy-1,4-pregnadiene-11.beta.,21-diol-3,20-dione 21-acetate.
CROSS REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of copending application Ser. No. 753,256 filed Dec. 12, 1976 now abandoned.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
2819264 |
Gould et al. |
Jan 1958 |
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Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
753256 |
Dec 1976 |
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