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

Document Type: Research article

Authors

Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

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.

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