Bifunctional AKR1C3 inhibitors/androgen receptor modulators and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10071953-B2
Application number	US-201614993742-A
Country	US
Kind code	B2
Filing date	Jan 12, 2016
Priority date	Apr 13, 2011
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

The invention includes compositions comprising selective AKR1C3 inhibitors. The invention also includes compositions comprising bifunctional AKR1C3 inhibitors and selective androgen receptor modulators. The invention further includes methods of treatment using the compositions of the invention.

First claim

What is claimed is:

1. A compound of Formula (II) or a salt thereof:

wherein:
R 3 is nitro; and,
each occurrence of R 4 and R 5 is independently selected from the group consisting of H, C 1 -C 6 alkyl, haloalkyl, halogen, —CN, C 1 -C 6 alkoxy, —C(═O)H, —C(═O)OH, —C(═O)—(C 1 -C 6 alkyl), and SO 3 H.

2. The compound of claim 1 , wherein each occurrence of R 4 is independently selected from the group consisting of H, methyl, tert-butyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and acetyl.

3. The compound of claim 1 , wherein each occurrence of R 5 is independently selected from the group consisting of H, methyl, tert-butyl, methoxy, fluoro, chloro, bromo, trifluoromethyl, and acetyl.

4. A pharmaceutical composition comprising at least one compound of claim 1 and a pharmaceutically acceptable carrier.

5. The pharmaceutical composition of claim 4 , further comprising at least one therapeutic agent selected from the group consisting of indomethacin, desatinib, selegiline, seliciclib, TOK-001, SAHA, docetaxel, bevacizumab, taxotere, thalidomide, prednisone, Sipuleucel-T, cabazitaxel, MDV3100, ARN-509, abiraterone, temozolomide, tamoxifen, anastrozole, letrozole, vorozole, exemestane, fadrozole, formestane, raloxifene, any mixtures thereof, and any salts thereof.

6. The compound 3-((4-nitronaphthalen-1-yl)amino)benzoic acid, or a salt thereof:

7. A pharmaceutical composition comprising the compound of claim 6 and a pharmaceutically acceptable carrier.

8. The pharmaceutical composition of claim 7 , further comprising at least one therapeutic agent selected from the group consisting of indomethacin, desatinib, selegiline, seliciclib, TOK-001, SAHA, docetaxel, bevacizumab, taxotere, thalidomide, prednisone, Sipuleucel-T, cabazitaxel, MDV3100, ARN-509, abiraterone, temozolomide, tamoxifen, anastrozole, letrozole, vorozole, exemestane, fadrozole, formestane, raloxifene, any mixtures thereof, and any salts thereof.

Assignees

• Univ Pennsylvania

Inventors

• Penning Trevor M
• Adeniji Adegoke O
• Byrns Michael C
• Winkler Jeffrey
• Twenter Barry

Classifications

• C07C229/58 Primary

  having the nitrogen atom of at least one of the amino groups further bound to a carbon atom of a six-membered aromatic ring, e.g. N-phenyl-anthranilic acids · CPC title

• A61K31/195

  having an amino group · CPC title

• A61K31/196

  the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil · CPC title

• A61K31/205

  Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine · CPC title

• A61K31/405

  Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin · CPC title