Nuclear receptor modulators and their use for the treatment and prevention of cancer

Patent metadata

Field	Value
Publication number	US-10071945-B2
Application number	US-201214126178-A
Country	US
Kind code	B2
Filing date	Jun 15, 2012
Priority date	Jun 15, 2011
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R 1 to R 5 and X 1 to X 5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

First claim

The invention claimed is:

1. A method of inhibiting androgen-independent AR activation in a human subject that has prostate cancer, comprising administering to the subject an effective amount of a compound of Formula I:

wherein R 1 to R 5 are the same or different and are each selected from H and C 1 -C 6 alkoxy;
wherein X 1 to X 5 are the same or different and are each selected from H and the electron withdrawing groups of NO 2 , CN, and CF 3 ; and
wherein bond “a ” can be in either the E or Z form;
with the provisio that R 1 to R 5 and X 1 to X 5 cannot all be H simultaneously;

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

2. A method of inhibiting progesterone receptor (PR) and/or estrogen receptor (ER) activation in a human subject comprising administering to the subject an effective amount of a compound of Formula I:

wherein R 1 to R 5 are the same or different and are each selected from H and C 1 -C 6 alkoxy;
wherein X 1 to X 5 are the same or different and are each selected from H and the electron withdrawing groups of NO 2 , CN, and CF 3 ; and
wherein bond “a ” can be in either the E or Z form;
with the provisio that R 1 to R 5 and X 1 to X 5 cannot all be H simultaneously;

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

3. A method of modulating Hsp40 in a human subject comprising administering to the subject an effective amount of a compound of Formula I:

wherein R 1 to R 5 are the same or different and are each selected from H and C 1 -C 6 alkoxy;
wherein X 1 to X 5 are the same or different and are each selected from H and the electron withdrawing groups of NO 2 , CN, and CF 3 ; and
wherein bond “a ” can be in either the E or Z form;
with the proviso that R 1 to R 5 and X 1 to X 5 cannot all be H simultaneously;
or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof.

4. The method of claim 1 , wherein the compound is one of the following:

5. The method of claim 1 , wherein the compound is one of the following:

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

7. The method of claim 2 , wherein the compound is one of the following:

8. The method of claim 2 , wherein the compound is one of the following:

9. The method of claim 2 , wherein the compound is

10. The method of claim 3 , wherein the compound is one of the following:

Assignees

• Neckers Jane B
• Kim Yeong Sang
• Lee Sunmin
• Kumar Vineet
• Malhotra Sanjay V
• Us Health

Inventors

• Neckers Jane B
• Kim Yeong Sang
• Lee Sunmin
• Kumar Vineet
• Malhotra Sanjay V

Classifications

• C07C49/80

  containing halogen · CPC title

• C07C49/796 Primary

  polycyclic · CPC title

• C07C49/84

  containing ether groups, [IMAGE cpc-sch-C07C-0958.gif] groups,[IMAGE cpc-sch-C07C-0959.gif] groups, or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/12

  Ketones · CPC title