A new series of 1,2-diaryl-4,5,6,7-tetrahydro-1H-benzo [d]imidazoles, possessing a methylsulfonyl pharmacophore, were synthesized to evaluate their biological activities as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition studies were carried out to acquire structure-activity relationship data with respect to the point that molecular modeling studies showed that designed compounds bind in the primary binding site such that the SO 2 Me substituent at para-position of C-2 phenyl ring inserts into the 2°pocket present in COX-2 enzyme. COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC 50 values in the highly potent 0.34-0.69 lM range, and COX-2 selectivity indexes in the 52.3-163.8 range. 1-(4-Fluorophenyl)-2-(4-(methylsulfonyl)phenyl)-4,5,6,7-tetrahydro-1H-benzo[d] imidazole was identified as the most potent (IC 50 = 0.34 lM), and selective (SI = 163.8), COX-2 inhibitor among the synthesized compounds.