Selective testicular 11beta-HSD inhibitors and methods of use thereof

• US 20050020550A1
• Filed: 04/29/2004
• Published: 01/27/2005
• Est. Priority Date: 04/29/2003
• Status: Abandoned Application

• Current Assignee: David J. Morris, Matthew P. Hardy, Syed Abdul Latif
• Original Assignee: David J. Morris, Matthew P. Hardy, Syed Abdul Latif
• Inventors: Hardy, Matthew P., Latif, Syed Abdul, Morris, David J.
• Application Number:
  US10/835,890
• Publication Number:
  US 20050020550A1
• Time in Patent Office: Days
• US Class Current: 514/177
• CPC Class Codes: A61K 31/56 Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids

Abstract

Methods for increasing and decreasing male fertility using selective 11β-HSD1-dehydrogenase, 11β-HSD1-reductase and 11β-HSD2 dehydrogenase modulating compounds are described.

Claims

1. A method for increasing male fertility, comprising administering an effective amount of a 11β

-HSD1 reductase inhibitor to a subject, such that said fertility is increased.

3. The method of claim 1, wherein said 11β

-HSD1 reductase inhibitor is selective for testicular 11β

-HSD1 reductase.

19. The method of of claim 1, wherein said subject is a human.

20. The method of claim 1, further comprising administering a pharmaceutically acceptable carrier.

2. A method for increasing testosterone levels in a subject, comprising administering to said subject an effective amount of a 11β

-HSD1 reductase inhibitor, such that testosterone levels in said subject are increased.

4. The method of claim 2, wherein said 11β

-HSD1 reductase inhibitor is a steroid or a derivative thereof.

5. The method of claim 4, wherein said steroid is an 11-keto steroid.

6. The method of claim 5, wherein said 11-keto steroid is 11-keto-progesterone, 11-keto-testosterone, 11-keto-androsterone, 11-keto androstenedione, or 11-keto dehydroepiandrostenedione.

7. The method of claim 4, wherein said steroid is 3α

,5α

-reduced or 3α

,5β

-reduced.

8. The method of claim 7, wherein said steroid is 3α

,5α

-reduced-11-ketoprogesterone, 3α

,5α

-reduced-11-keto-testosterone, 3α

,5α

-reduced-11-keto-androstenedione, 3α

,5α

-tetrahydro-11-dehydro-corticosterone, 3α

,5α

-reduced-11-keto-androsterone, 3α

,5α

-tetrahydro-progesterone, 3α

,5α

-tetrahydro-testosterone, 3α

,5α

-tetrahydro-deoxycorticosterone, 3α

,5β

-tetrahydro-deoxycorticosterone or 3α

,5α

-reduced-11-keto dehydroepiandrostenedione.

9. The method of claim 4, wherein said steroid is 5α

-reduced.

10. The method of claim 9, wherein said steroid is 5α

-reduced-11-ketoprogesterone, 5α

-reduced-11-keto-testosterone, 5α

-reduced-11-keto-androstenedione, 5α

-reduced-11-dehydro-corticosterone, 5α

-reduced-11-keto-androsterone, or 5α

-reduced-11-keto dehydroepiandrostenedione.

11. A method for decreasing male fertility, comprising administering to a subject an effective amount of a 11β

-HSD1 dehydrogenase inhibitor, such that said fertility is decreased.

13. The method of claim 11, wherein said 11β

-HSD1 dehydrogenase inhibitor is selective for testicular 11β

-HSD1 dehydrogenase.

14. The method of claim 11, wherein said steroid is 11β

-hydroxy testosterone, 11β

-hydroxy androstenedione, 11β

-hydroxy dehydroepiandrostenedione, 11β

-progesterone, or chenodeoxycholic acid.

15. The method of claim 11, wherein said 11β

-HSD1 dehydrogenase inhibitor is a 3α

,5β

-reduced steroid, a 3α

,5α

-reduced steroid, or a 5α

-reduced steroid.

16. The method of claim 15, wherein said steroid is 3α

,5α

-reduced-11β

-hydroxy testosterone, 3α

,5α

-reduced-11-hydroxy androstenedione, 3α

,5α

-reduced-11β

-hydroxy dehydroepiandrostenedione, 3α

,5α

-reduced-corticosterone, 3α

,5α

-reduced-aldosterone, 3α

,5β

-tetrahydro-deoxycorticosterone, 3α

,5β

-tetrahydro-progesterone, 3α

, 5β

-tetrahydro-testosterone, 3α

,5α

-tetrahydro-deoxycorticosterone, or 3α

,5α

-reduced-11β

-progesterone.

17. The method of claim 15, wherein said steroid is 5α

-reduced-11β

-hydroxy testosterone, 5α

-reduced-11β

-hydroxy androstenedione, 5α

-reduced-11β

-hydroxy dehydroepiandrostenedione, or 5α

-reduced-11β

-progesterone.

18. The method of claim 15, wherein said steroid is 3α

, 5β

-reduced-11β

-OH-progesterone, or 3α

,5β

-reduced-11β

-OH-testosterone.

12. A method for decreasing testosterone levels in a subject, comprising administering to a subject an effective amount of a 11β

-HSD1 dehydrogenase inhibitor, such that testosterone levels in said subject are decreased.

21. A pharmaceutical composition comprising an effective amount of 11-keto-progesterone, 11-keto-testosterone, 11-keto-androsterone, 11-keto androstenedione, 11-keto dehydroepiandrostenedione, 3α

,5α

-reduced-11-ketoprogesterone, 3α

,5α

-reduced-11-keto-testosterone, 3α

,5α

-reduced-11-keto-androstenedione, 3α

,5α

-tetrahydro-11-dehydro-corticosterone, 3α

, 5α

-reduced-11-keto-androsterone, 3α

, 5α

-reduced-11-keto dehydroepiandrostenedione, 5α

-reduced-11-ketoprogesterone, 5α

-reduced-11-keto-testosterone, 5α

-reduced-11-keto-androstenedione, 5α

-reduced-11-dehydro-corticosterone, 5α

-reduced-11-keto-androsterone, 5α

-reduced-11-keto dehydroepiandrostenedione, 3α

,5β

-tetrahydro-deoxycorticosterone, 3α

,5α

-tetrahydro-progesterone, 3α

,5α

-tetrahydro-testosterone, 3α

,5α

-tetrahydro-deoxycorticosterone, or a pharmaceutically acceptable salt, ester, or prodrug thereof and a pharmaceutically acceptable carrier, wherein said effective amount is effective to increase male fertility.

22. A pharmaceutical composition comprising an effective amount of 11β

-hydroxy testosterone, 11β

-hydroxy androstenedione, 11β

-hydroxy dehydroepiandrostenedione, 11β

-progesterone, chenodeoxycholic acid, 3α

,5α

-reduced-11β

-hydroxy testosterone, 3α

, 5α

-reduced-11-hydroxy androstenedione, 3α

,5α

-reduced-11β

-hydroxy dehydroepiandrostenedione, 3α

,5α

-reduced-corticosterone, 3α

,5α

-reduced-aldosterone, 3α

, 5α

-reduced-11β

-progesterone, 5α

-reduced-11β

-hydroxy testosterone, 5α

-reduced-11β

-hydroxy androstenedione, 5α

-reduced-11β

-hydroxy dehydroepiandrostenedione, 5α

-reduced-11β

-progesterone, 3α

,5β

-reduced-11β

-OH-progesterone, 3α

,5β

-reduced-11β

-OH-testosterone, 3α

,5β

-tetrahydro-deoxycorticosterone, 3α

,5β

-tetrahydro-progesterone, 3α

,5β

-tetrahydro-testosterone, 3α

,5α

-tetrahydro-deoxycorticosterone, 3α

, 5β

-chenodeoxycholic acid or a pharmaceutically acceptable salt, prodrug, or ester thereof and pharmaceutically acceptable carrier, wherein said effective amount is effective to decrease male fertility.