Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2

Abstract

New pyrazole and pyrazoline derivatives have been synthesized and their ability to inhibit ovine COX-1/COX-2 isozymes was evaluated using in vitro cyclooxygenase (COX) inhibition assay. Among the tested compounds, N-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)methylene) -3,5-bis(trifluoromethyl)aniline 8d exhibit optimal COX-2 inhibitory potency (IC 50 = 0.26 lM) and selectivity (SI) = >192.3] comparable with reference drug celecoxib (IC 50 value of 0.28 lM and selectivity index of 178.57). Moreover, the anti-inflammatory activity of selected compounds, which are the most selective COX-2 inhibitors in the COX inhibition assay, was investigated in vivo using carrageenan-induced rat paw edema model. Molecular modeling was conducted to study the ability of the active compounds to bind into the active site of COX-2 which revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. © 2012 Elsevier Ltd. All rights reserved.