Design and synthesis of new 1,2-diaryl-4,5,6,7-tetrahydro-1H-benzo[d] imidazoles as selective cyclooxygenase (COX-2) inhibitors

• Published in: Medicinal chemistry research 2012-08, Vol.21 (8), p.1869-1875
• Main Authors: Zarghi, A., Reihanfard, H., Arfaei, S., Daraei, B., Hedayati, M.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-011-9709-y

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 μM 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 μM), and selective (SI = 163.8), COX-2 inhibitor among the synthesized compounds.