2,5-Diaryl-1,3,4-oxadiazoles as selective COX-2 inhibitors and anti-inflammatory agents

Abstract

A new series of compounds comprising of 2,5-diaryl-1,3,4-oxadiazoles was synthesized and evaluated as potential COX-2 inhibitors. Compounds 6b, 6e, 6f, 7e and 7f were found to be the most potent and selective inhibitors of COX-2 (IC₅₀ = 0.48–0.89 μM; SI = 67.96–132.83). Compounds 6e, 6f and 7f displayed anti-inflammatory activity superior to celecoxib in a carrageenan-induced rat paw edema assay. Structure–activity relationship analysis suggested that the compounds with methylsulfonyl moieties lead to more selective inhibition of COX-2, which is well supported by molecular docking studies. Cytotoxicity studies of the most potent compounds in RAW 264.7 and J774A.1 cells revealed cell viabilities of more than 89% when tested at the concentration of 30 μM.