The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Aug. 04, 2015

Filed:

Dec. 12, 2011
Applicants:

Bruce D. Hammock, Davis, CA (US);

Sung Hee Hwang, Davis, CA (US);

Karen Wagner, Davis, CA (US);

Christophe Morisseau, West Sacramento, CA (US);

Aaron Wecksler, Davis, CA (US);

Guodong Zhang, Davis, CA (US);

Inventors:

Bruce D. Hammock, Davis, CA (US);

Sung Hee Hwang, Davis, CA (US);

Karen Wagner, Davis, CA (US);

Christophe Morisseau, West Sacramento, CA (US);

Aaron Wecksler, Davis, CA (US);

Guodong Zhang, Davis, CA (US);

Assignee:
Attorney:
Primary Examiner:
Int. Cl.
CPC ...
A61K 31/635 (2006.01); C07D 231/10 (2006.01); C07D 231/12 (2006.01); C07D 231/40 (2006.01); C07D 231/14 (2006.01);
U.S. Cl.
CPC ...
C07D 231/12 (2013.01); C07D 231/14 (2013.01); C07D 231/40 (2013.01);
Abstract

The present invention provides compounds and compositions, e.g., a series of compounds wherein a 1,5-biarylpyrazole group is conjugated to a urea group by a non-cleavable covalent chain, that are useful as dual COX-2/sEH inhibitors. The compounds disclosed herein have activity associated with the arachidonate cascade. The activity of these compounds was demonstrated using a lipopolysaccharide (LPS) induced model of pain in the rat. The compounds of the present invention demonstrated superior anti-allodynic activity as compared to the same dose of celecoxib, i.e., a COX-2 inhibitor, also as compared to the same dose of t-AUCB, i.e., a sEH inhibitor, and also as compared to the co-administered same dose of both celecoxib and t-AUCB. The dual inhibitors of the present invention demonstrate enhanced in vivo anti-allodynic activity in a nociceptive behavioral assay. In addition, the compounds of the present invention also demonstrated to have potent anti-angiogenic effects toward endothelial cells (HUVEC) and inhibit angiogenesis in vitro, ex vivo and in vivo. The dual inhibitors of the present invention also demonstrate anti-angiogenic effect to slow breast tumor growth in vivo.


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