Synthesis and bioevaluation of 2-phenyl-5-methyl-2H-1,2,3-triazole-4-carboxylic acid/carbohydrazide derivatives as potent xanthine oxidase inhibitors

A series of 2-phenyl-5-methyl-2H-1,2,3-triazole-4-carboxylic acids/carbohydrazides as analogues of febuxostat were synthesized and evaluated for their in vitro xanthine oxidase (XO) inhibitory activity. Among these compounds, the carboxylic acid derivatives 7a-h and 8a-h exhibited high potency in the submicromolar/nanomolar range. Steady-state kinetics experiment revealed that 7f was a mixed-type inhibitor of xanthine oxidase. In addition, a molecular docking study of 7f was performed to determine its binding mode at the active site of xanthine oxidase.