.

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: 5,998,427

« Back to Dashboard

Claims for Patent: 5,998,427

Title: Androstenones
Abstract:The present invention relates to compounds of formula (I), wherein carbons 1 and 2 are joined by either a single or a double bond; R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or methyl; R.sup.3 is (B) wherein X, R.sup.6, R.sup.7 and R.sup.8 are various groups, and pharmaceutically acceptable solvates thereof and their use in the treatment of androgen responsive and mediated diseases. ##STR1##
Inventor(s): Batchelor; Kenneth William (Durham, NC), Frye; Stephen Vernon (Durham, NC)
Assignee: Glaxo Wellcome Inc. (Research Triangle Park, NC)
Application Number:09/078,468
Patent Claims: 1. A compound of formula (I) ##STR17## wherein carbons 1 and 2 are joined by either a single or a double bond; R.sup.1 is hydrogen or methyl;

R.sup.2 is hydrogen or methyl;

R.sup.3 is (B) ##STR18## wherein R.sup.6 is trifluoromethyl, phenyl optionally substituted with one or more halogens or branched (C.sub.4-7) alkyl groups, or branched (C.sub.4-7) alkyl;

either of R.sup.7 or R.sup.8 is trifluoromethyl, halogen, phenyl optionally substituted with one or more halogens or branched (C.sub.4-7)alkyl groups, or branched (C.sub.4-7)alkyl, while the other is hydrogen or halogen; and

X is hydrogen or halogen,

or a pharmaceutically acceptable solvate thereof.

2. A compound as claimed in claim 1 wherein X is hydrogen.

3. A compound as claimed in claim 1 wherein R.sup.2 is hydrogen.

4. A compound as claimed in claim 1 wherein R.sup.6 is trifluoromethyl, phenyl optionally substituted with one or more halogens, or branched (C.sub.4-7) alkyl; and either of R.sup.7 or R.sup.8 is trifluoromethyl, halogen, phenyl optionally substituted with one or more halogens, or branched (C.sub.4-7) alkyl, while the other is hydrogen or halogen.

5. A compound as claimed in claim 1 wherein carbons 1 and 2 are joined by a double bond.

6. A compound as claimed in claim 1 of formula (IB); ##STR19## wherein carbons 1 and 2 are joined by either a single or a double bond; R.sup.1 is hydrogen or methyl;

R.sup.6 is trifluoromethyl, phenyl optionally substituted with one or more halogens, or branched (C.sub.4-7) alkyl;

either of R.sup.7 or R.sup.8 is trifluoromethyl, halogen, phenyl optionally substituted with one or more halogens, or branched (C.sub.4-7) alkyl, while the other is hydrogen or halogen; and

X is hydrogen or halogen.

7. A compound as claimed in claim 6 wherein when R.sup.7 or R.sup.8 is branched (C.sub.4-7) alkyl and X is hydrogen, R.sup.6 is trifluoromethyl or phenyl optionally substituted with one or more halogens.

8. A compound as claimed in claim 6 wherein R.sup.6 is trifluoromethyl or branched (C.sub.4-7) alkyl; and either of R.sup.7 or R.sup.8 is trifluoromethyl, halogen, or phenyl substituted with one or more halogens, while the other is hydrogen or halogen.

9. A compound as claimed in claim 8 wherein R.sup.6 is trifluoromethyl or branched (C.sub.4-7) alkyl; either of R.sup.7 or R.sup.8 is trifluoromethyl while the other is hydrogen; and X is hydrogen.

10. A compound as claimed in claim 6 wherein R.sup.6 and R.sup.8 are independently trifluoromethyl or t-butyl, while R.sup.7 and X are hydrogen.

11. A pharmaceutical formulation comprising an effective amount of a compound as claimed in claim 1 a pharmaceutically acceptable carrier thereof.

12. A process for preparing a compound as claimed in claim 1 which comprises:

(A) for compounds of formula (I) wherein carbons 1 and 2 are joined by a single bond, hydrogenating a compound of formula (IVa) ##STR20## (B) for compounds of formula (I) wherein carbons 1 and 2 are joined by a double bond, reacting a compound of formula (V) ##STR21## with a compound of formula (IIa)

and if necessary and/or desired, subjecting the compound thus obtained to one or more further reactions comprising:

(i) interconversion to another compound of formula (I);

(ii) removing any protecting group or groups; and/or

(iii) converting the compound of formula (I) or a solvate thereof into a pharmaceutically acceptable solvate thereof.

13. A process as claimed in claim 12 wherein in process (B) the compound of formula (V) is treated with a halogenating agent in the presence of a base prior to reaction with a compound of formula (IIa).

14. A process as claimed in claim 12 wherein in step (i) a compound of formula (I) wherein there is a double bond between carbons 1 and 2 and wherein R.sup.2 is hydrogen is prepared by dehydrogenating a compound of formula (Ia). ##STR22##

15. A method of inhibiting 5.alpha.-testosterone reductase enzyme comprising contacting said enzyme with an effective 5.alpha.-testosterone inhibitory amount of a compound as claimed in claim 1.

16. A method of treating an androgen responsive or mediated disease in a mammal suffering from said disease comprising administering to said mammal, an effective androgen responsive or mediated disease amount of a compound as claimed in claim 1.

17. A method of claim 16 wherein the androgen responsive or mediated disease is benign prostatic hyperplasia, prostate cancer, acne, male pattern baldness and hirsutism.

18. A compound of formula (IVa) wherein R.sup.1 and R.sup.2 are independently hydrogen or methyl and R.sup.3 is as defined in claim 1, or a solvate thereof.

19. The compound of claim 1 wherein said compound is selected from the group consisting of: 17.beta.-N-(2,5-bis(Trifluoromethyl))phenylcarbamoyl-4-aza-5.alpha.-andros tan-3-one, 17.beta.-N-(2,5-bis(Trifluoromethyl))phenylcarbamoyl-4-methyl-4-aza-5.alph a.-androstan-3-one, 17.beta.-N-(2-t-Butyl-5-trifluoromethyl)phenylcarbamoyl-4-aza-5.alpha.-and rost-1-en-3-one, 17.beta.-N-(2-t-Butyl-5-trifluoromethyl)phenylcarbamoyl-4-aza-5.alpha.-and rostan-3-one, 17.beta.-N-(2-t-Butyl-5-trifluoromethyl)phenylcarbamoyl-4-methyl-4-aza-5.a lpha.-androstan-3-one, 17.beta.-N-(2,5-Di-t-butyl)phenylcarbamoyl-4-aza-5.alpha.-androst-1-en-3-o ne, 17.beta.-N-(2,5-Di-t-butyl)phenylcarbamoyl-4-aza-5.alpha.-androstan-3-one, 17.beta.-N-(2,5-Di-t-butyl)phenylcarbamoyl-4-methyl-4-aza-5.alpha.-androst an-3-one, 17.beta.-N-(2,5-bis(Trifluoromethyl)phenylcarbamoyl-4-aza-7.beta.-methyl-5 .alpha.-androst-1-en-3-one, and 17.beta.-N-(2-t-Butyl-5-trifluoromethyl)phenylcarbamoyl-4-aza-7.beta.-meth yl-5.alpha.-androst-1-en-3-one.
« Back to Dashboard

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

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