Synthesis and structure− activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase

SH Hwang, KM Wagner, C Morisseau…

Index: Hwang, Sung Hee; Wagner, Karen M.; Morisseau, Christophe; Liu, Jun-Yan; Dong, Hua; Wecksler, Aaron T.; Hammock, Bruce D. Journal of Medicinal Chemistry, 2011 , vol. 54, # 8 p. 3037 - 3050

Full Text: HTML

Citation Number: 61

Abstract

A series of dual inhibitors containing a 1, 5-diarylpyrazole and a urea were designed, synthesized, and evaluated as novel COX-2/sEH dual inhibitors in vitro using recombinant enzyme assays and in vivo using a lipopolysaccharide (LPS) induced model of pain in rats. The best inhibition potencies and selectivity for sEH and COX-2 over COX-1 were obtained with compounds (21b, 21i, and 21j) in which both the 1, 5-diaryl-pyrazole group and the ...