Invention Grant
- Patent Title: Pyrazole inhibitors of COX-2 and sEH
- Patent Title (中): 吡唑类抑制剂COX-2和sEH
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Application No.: US13993317Application Date: 2011-12-12
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Publication No.: US09096532B2Publication Date: 2015-08-04
- Inventor: Bruce D. Hammock , Sung Hee Hwang , Karen Wagner , Christophe Morisseau , Aaron Wecksler , Guodong Zhang
- Applicant: Bruce D. Hammock , Sung Hee Hwang , Karen Wagner , Christophe Morisseau , Aaron Wecksler , Guodong Zhang
- Applicant Address: US CA Oakland
- Assignee: The Regents of the University of California
- Current Assignee: The Regents of the University of California
- Current Assignee Address: US CA Oakland
- Agency: Kilpatrick Townsend and Stockton LLP
- International Application: PCT/US2011/064474 WO 20111212
- International Announcement: WO2012/082647 WO 20120621
- Main IPC: A61K31/635
- IPC: A61K31/635 ; C07D231/10 ; C07D231/12 ; C07D231/40 ; C07D231/14

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.
Public/Granted literature
- US20140038923A1 PYRAZOLE INHIBITORS OF COX-2 AND SEH Public/Granted day:2014-02-06
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