.

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: 4,335,121

« Back to Dashboard

Claims for Patent: 4,335,121

Title: Androstane carbothioates
Abstract:Compounds of the formula ##STR1## wherein R.sup.1 represents a fluoro-, chloro- or bromo-methyl group or a 2'-fluoroethyl group, R.sup.2 represents a group COR.sup.6 where R.sup.6 is a C.sub.1-3 alkyl group or OR.sup.2 and R.sup.3 together form a 16.alpha.,17.alpha.-isopropylidenedioxy group; R.sup.3 represents a hydrogen atom, a methyl group (which may be in either the .alpha.- or .beta.-configuration) or a methylene group; R.sup.4 represents a hydrogen, chlorine or fluorine atom; R.sup.5 represents a hydrogen or fluorine atom and symbol represents a single or double bond have good anti-inflammatory activity, particularly on topical applications. The compounds of formula I are prepared by esterification, halogenation, reduction, deprotection and reaction at a 9,11-double bond to form a 9.alpha.-halo-11.beta.-hydroxy grouping. Pharmaceutical compositions containing the compounds of formula I and methods for the use of the compounds are described and claimed.
Inventor(s): Phillipps; Gordon H. (Wembley, GB2), Bain; Brian M. (Chalfont St. Peter, GB2), Steeples; Ian P. (Ruislip Manor, GB2), Williamson; Christopher (Cobham, GB2)
Assignee: Glaxo Group Limited (London, GB2)
Application Number:06/234,113
Patent Claims: 1. Compounds of the formula ##STR5## wherein R.sup.1 represents a fluoro-, chloro- or bromo-methyl group or a 2'-fluoroethyl group, R.sup.2 represents a group COR.sup.6 where R.sup.6 is a C.sub.1-3 alkyl group or OR.sup.2 and R.sup.3 together form a 16.alpha.,17.alpha.-isopropylidenedioxy group; R.sup.3 represents a hydrogen atom, a methyl group (which may be in either the .alpha.- or .beta.- configuration) or a methylene group; R.sup.4 represents a hydrogen, chlorine or fluorine atom; R.sup.5 represents a hydrogen or fluorine atom and the symbol represents a single or double bond.

2. Compounds as claimed in claim 1 in which R.sup.1 is a chloromethyl or fluoromethyl group.

3. Compounds as claimed in claim 1 in which R.sup.4 is fluorine.

4. Compounds as claimed in claim 1 which are 1,4-dienes.

5. Compounds as claimed in claim 2 which are 1,4-dienes wherein R.sup.4 and R.sup.5 are fluorine and R.sup.3 is .alpha.- or .beta.-methyl or methylene.

6. Compounds as claimed in claim 5 which are 1,4-dienes wherein R.sup.3 is .alpha.-methyl group.

7. A compound as claimed in claim 1 which is

S-chloromethyl 9.alpha.-fluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propiony loxyandrosta-1,4-diene-17.beta.-carbothioate.

8. S-chloromethyl 6.alpha., 9.alpha.-difluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propio nyloxyandrosta-1,4-diene-17.beta.-carbothioate.

9. Pharmaceutical compositions for topical use in antiinflammatory therapy, comprising at least one androstane compound of formula I as defined in claim 1, together with one or more pharmaceutical carriers or excipients.

10. A method of treating inflammation which comprises administering, to a subject suffering from inflammation, an effective amount of a compound of formula I as defined in claim 1.

11. A compound as claimed in claim 1 which is S-chloromethyl 9.alpha.-fluoro-11.beta.-hydroxy-16-methylene-3-oxo-17.alpha.-propionyloxy androsta-1,4-diene-17.beta.-carbothioate.

12. A compound as claimed in claim 1 which is S-fluoromethyl 6.alpha., 9.alpha.-difluoro-11.beta.-hydroxy-16.alpha., 17.alpha.-isopropylidenedioxy-3-oxoandrosta-1,4-diene-17.beta.-carbothioat e.

13. A compound as claimed in claim 1 which is S-fluoromethyl 6.alpha., 9.alpha.-difluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propio nyloxyandrosta-1,4-diene-17.beta.-carbothioate.

14. Compounds as claimed in claim 5 wherein R.sup.2 is acetyl or propionyl.

15. A pharmaceutical composition as claimed in claim 9 wherein the active compound is S-chloromethyl 6.alpha., 9.alpha.-difluoro-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-17.alpha.-propio nyloxyandrosta-1,4-diene-17.beta.-carbothioate.

16. A pharmaceutical composition as claimed in claim 9 wherein R.sup.1 is a chloromethyl or fluoromethyl group, R.sup.4 and R.sup.5 are fluorine, R.sup.3 is .alpha.- or .beta.-methyl or methylene and the compound is a 1,4-diene.

17. A method of treating inflammation which comprises administering, to a subject suffering form inflammation, an effective amount of the composition of claim 15.

18. A method of treating inflammation which comprises administering, to a subject suffering from inflammation, an effective amount of the composition of claim 16.

19. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but containing either a free 17.beta.-carbothioic acid group (or salt thereof) or a free 17.alpha.-hydroxy group (R.sup.3 being a hydrogen atom or a methyl or methylene group), any other reactive groups present optionally being in protected form, is subjected to esterification.

20. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but containing a 17.beta.-substituent of formula --COS(CH.sub.2).sub.n Y (wherein Y represents a displaceable substituent and n is 1 or 2) is reacted with a compound serving to replace the group Y by a halogen atom, whereby a compound of formula I as claimed in claim 1 is formed.

21. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but carrying an 11-oxo group is subjected to reduction to form the required 11.beta.-hydroxy androstane.

22. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but carrying a protected 11.beta.-hydroxy group is subjected to deprotection.

23. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but having a 9,11-double bond, and no substituent in the 11-position, is reacted with an N-bromoamide or -imide followed by treatment of the bromohydrin thus obtained with a base to form the corresponding 9,11-epoxide, which epoxide is reacted with hydrogen fluoride or hydrogen chloride whereby a compound of formula I as claimed in claim 1 is formed containing a 9.alpha.-fluoro-11 hydroxy or 9-chloro-11.beta.-hydroxy grouping.

24. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 but having a 9,11-double bond and no substituent in the 11-position, is reacted with an N-chloro-amide or -imide whereby a compound as claimed in claim 1 is obtained which contains 9.alpha.-chloro-11.beta.-hydroxy grouping.

25. A process for the preparation of compounds as claimed in claim 1 in which a compound corresponding to formula I as defined in claim 1 in which represents a double bond is subjected to partial reduction to produce a corresponding compound in which represents a single bond.
« 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