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

In this study, a new series of 5-substituted 1-benzyl-2-(methylsulfonyl)-1-H-imidazole with atypical structure-activity relationship was designed, synthesized, and biological evaluated as selective cyclooxygenase-2 inhibitors. Docking studies revealed that although the pharmacophoric substitute of the compound 5b, methylsulfonyl group, has been directly attached 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 with Arg513 is established. Also, additional hydrogen binding could form between NH of anilino moiety of the 5b and Arg120. All of the compounds had selective inhibitory activity against cyclooxygenase-2 in micromolar concentrations comparable with the reference, Celecoxibe. Finally, compound 5b with the selectivity index 115 and IC50 of 0.71 μM against cyclooxygenase-2 was the most potent one.