.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Claims for Patent: 4,124,707

« Back to Dashboard

Claims for Patent: 4,124,707

Title: 7.alpha.-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor
Abstract:Novel 3,20-dioxo-7.alpha.-halogeno-1,4-pregnadienes are described and their use as anti-inflammatory agents. Preferred are 7.alpha.-bromo- and 7.alpha.-chloro- derivatives, particularly 7.alpha.-bromo- and 7.alpha.-chloro-1,4-pregnadienes-11.beta.,17.alpha.,21-triol-3,20-dione 17,21-dihydrocarboncarboxylates, the 16-methyl and 16-methylene derivatives thereof being particularly valuable as topical anti-inflammatory agents.
Inventor(s): Green; Michael J. (Kendall Park, NJ), Shue; Ho-Jane (Belleville, NJ)
Assignee: Schering Corporation (Kenilworth, NJ)
Application Number:05/848,856
Patent 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-tri ol-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-trio l-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-trio l-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.a lpha.,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-tri ol-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-trio l-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-trio l-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-tri ol-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.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc