Design, synthesis, and biological evaluation of substituted 2-alkylthio-1,5-diarylimidazoles as selective COX-2 inhibitors.

摘要

A new type of 1-aryl-5-(4-methylsulfonylphenyl)imidazoles, possessing C-2 alkylthio (SMe or SEt) substituents, were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 1-(4-bromophenyl)-5-(4-methylsulfonylphenyl)-2-methylthioimidazole (11g), was the most potent and selective COX-2 inhibitor (COX-2 IC(50)=0.43muM with no inhibition of COX-1 up to 25muM) relative to the reference drug celecoxib (COX-2 IC(50)=0.21muM with no inhibition of COX-1 up to 25muM) and also showed very good anti-inflammatory activity compared to celecoxib in carrageenan-induced rat paw edema assay.