Methods and compositions related to a retinoid receptor-selective pathway

Patent metadata

Field	Value
Publication number	US-9611235-B2
Application number	US-201113102475-A
Country	US
Kind code	B2
Filing date	May 6, 2011
Priority date	May 6, 2010
Publication date	Apr 4, 2017
Grant date	Apr 4, 2017

Abstract

Provided herein are methods and compositions related to a retinoid receptor-selective pathway. As described herein, this pathway can be targeted to manipulate a tumor microenvironment. For example, the methods and compositions described herein can be used to induce apoptosis in a cancer cell. Further, the compositions described herein, including Sulindac and analogs thereof, can be used to target this pathway for the treatment or prevention of cancer in human patients.

First claim

What is claimed is:

1. A compound of formula (I), or a sodium salt thereof, having the structure:

wherein A is a phenyl, and wherein A is substituted by one or two substituents independently selected from the group consisting of C2-3 alkyl, n-butyl, iso-butyl, sec-butyl, —CF 3 , a C3-C4 cycloalkyl, and a C4-C5 cycloalkylalkyl;
wherein B is a fused phenyl, and wherein B is substituted by a fluoro;
wherein R 1 is —(CR 5 R 6 ) n COOH;
wherein R 2 is CH 3 ;
wherein R 5 and R 6 are H; and
wherein n is 1 or 2.

2. A compound of formula (II), or a sodium salt thereof, having the structure:

wherein R 1 is selected from the group consisting of CH 2 COOH and CH 2 CH 2 COOH;
wherein R 2 is CH 3 ; and
wherein R 3 is selected from the group consisting of 4-CH 2 CH 3 , and 4-CH(CH 3 ) 2 .

3. The compound of claim 2 , or a sodium salt thereof, selected from the group consisting of:

4. The compound of claim 2 , or a sodium salt thereof, selected from the group consisting of:

5. The compound of claim 2 , or a sodium salt thereof, having the structure:

6. A compound, or a sodium salt thereof, having the structure:

7. A pharmaceutical composition comprising a compound of claim 1 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.

8. A pharmaceutical composition comprising a compound of claim 2 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.

9. A pharmaceutical composition comprising a compound of claim 6 , or a sodium salt thereof, and a pharmaceutically acceptable excipient.

Assignees

• Zhang Xiao-Kun
• Su Ying
• Zhou Hu
• Liu Wen
• Huang pei-qiang
• Sanford-Burnham Medical Res Inst
• Univ Xiamen

Inventors

• Zhang Xiao-Kun
• Su Ying
• Zhou Hu
• Liu Wen
• Huang pei-qiang

Classifications

• G01N2333/70567

  Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors · CPC title

• A61K31/192 Primary

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title

• G01N2510/00

  Detection of programmed cell death, i.e. apoptosis · CPC title

• C07C57/62

  containing six-membered aromatic rings and other rings · CPC title

• A61K38/191

  Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta · CPC title