Xanthine oxidase (XO) is an important target for the treatment of hyperuricemia and gout. Based on the two known non-purine xanthine oxidase inhibitors, febuxostat and topiroxostat, 14 oxadiazole derivatives have been designed and synthesized. These compounds have been evaluated against XO and five of them exhibited significant inhibitory activities at the concentrations below 10 μmol·L(-1).