Pharmaceutical compositions which inhibit FKBP52-mediated regulation of androgen receptor function and methods of using same

Patent metadata

Field	Value
Publication number	US-9782399-B2
Application number	US-201514955505-A
Country	US
Kind code	B2
Filing date	Dec 1, 2015
Priority date	Sep 15, 2009
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

Pharmaceutical compositions that bind to a predicted FK506 Binding Protein 52 (FKBP52) interaction surface on the androgen receptor hormone binding domain, otherwise known as FKBP52 Targeting Agents (FTAs) are provided. These compositions of the present invention are found to specifically recognize the FKBP52 regulatory surface on the androgen receptor and inhibit FKBP52 from functionally interacting with the androgen receptor. Compositions comprising the pharmaceutical composition, as well as methods of use, treatment and screening are also provided.

First claim

The invention claimed is:

1. A method of reducing, suppressing, or inhibiting benign prostatic hyperplasia (BPH) in a male mammal, the method comprising: administering to the mammal in need thereof a pharmaceutical composition comprising a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof, wherein the composition comprises a pharmaceutically and physiologically acceptable carrier, in an amount effective to inhibit prostate cell growth in the mammal.

2. The method of claim 1 , wherein the pharmaceutical composition further comprises one or more anti-androgenic compounds and/or one or more luteinizing hormone-releasing hormone (LH-RH) agonists.

3. The method of claim 2 , wherein the one or more anti-androgenic compound(s) is/are selected from the group consisting of bicalutamide, nilutamide, and 5-alpha-reductase inhibitors.

4. The method of claim 3 , wherein the 5-alpha-reductase inhibitor(s) is/are selected from the group consisting of MK-906, 17-β-N,N-diethylcarbamoyl-4-methyl-4-aza-5-α-androstan-3-one, 4-azasteroid, 6-methylene-4-pregnene-3,20-dione, and 4-methyl-3-oxo-4-aza-5-α-pregnane-30(s) carboxylate.

5. The method of claim 1 , further comprising administering to the mammal in need thereof compound 1 or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein compound 1 is

6. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

7. The method of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt, solvate or stereoisomer thereof.

8. The method of claim 1 , further comprising administering to the mammal in need thereof compound 4 or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein compound 4 is

9. The method of claim 5 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

10. The method of claim 6 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

11. The method of claim 7 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

12. The method of claim 6 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

13. The method of claim 5 , wherein the method comprises administering to the mammal in need thereof

14. The method of claim 6 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

15. The method of claim 7 , further comprising administering to the mammal in need thereof a compound selected from the group consisting of:

and pharmaceutically acceptable salts, solvates and stereoisomers thereof.

16. The method of claim 5 , wherein the method comprises administering to the mammal in need thereof compound 2 or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein compound 2 is

17. The method of claim 7 , wherein the compound is

18. The method of claim 6 , wherein the compound is

19. The method of claim 6 , further comprising administering to the mammal in need thereof compound 1, wherein compound 1 is

Assignees

• Us Health
• The Regents Of The Univ Of California A California Corp
• Univ Texas
• Univ California
• Univ Texas

Inventors

• Neckers Leonard M
• Cox Marc B
• Neckers Jane B
• Kim Yeong Sang
• Iwai Aki
• Ning Yangmin
• Kugelman-Tonos Johanny
• Balsiger Heather A
• Fletterick Robert

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P5/28

  Antiandrogens · CPC title

• A61K31/165

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title

• C07C233/66

  having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups · CPC title