Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors

A new type of 4,5-diaryl-4H-1,2,4-triazole, possessing C-3 thio and alkylthio (SH, SMe or SEt) substituents, was designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 3-ethylthio-5-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-4H-1,2,4-triazole (10d), exhibited a high in vitro selectivity (COX-1 IC50 = 20.5 nM; COX-2 IC50 = 1.8 nM; SI = 11.39) relative to the reference drug celecoxib (COX-1 IC50 = 3.7 nM; COX-2 IC50 = 2.2 nM; SI = 1.68) and also showed good anti-inflammatory activity compared to celecoxib in a carrageenan-induced rat paw edema assay.

Design, synthesis, and evaluation of a novel class of diaryl-4H-1,2,4-triazoles, possessing C-3 thio and alkylthio (SH, SMe or SEt) substituents as selective cyclooxygenase-2 inhibitors (5a–n, 11a–f) are described.Figure optionsDownload as PowerPoint slide