Novel Group of Imidazole Derivatives as Atypical Selective Cyclooxygenase-2 Inhibitors: Design, Synthesis and Biological Evaluation

Abstract

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazolewith atypical structure-activity relationship was designed, synthesized, and biologicalevaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that althoughthe pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directlyattached to the central ring, it is in the same direction of the sulfonamide group of Celecoxib,a known selective cyclooxygenase-2 inhibitor. Therefore effective hydrogen binding withArg513 is established. Also, additional hydrogen binding could form between NH ofanilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activityagainst cyclooxygenase-2 in micromolar concentrations comparable with the reference,Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC50 of 0.71 μM againstcyclooxygenase-2 was the most potent one.