噁二唑类黄嘌呤氧化酶抑制剂的设计合成及活性评价

Design, synthesis and biological evaluation of oxadiazole derivatives as xanthine oxidase inhibitors

摘要: 黄嘌呤氧化酶(xanthine oxidase, XO)是治疗高尿酸血症及痛风的重要靶标。本文基于已上市的非嘌呤类XO抑制剂非布索坦(febuxostat)和托匹司他(topiroxostat),采用分子拼接和电子等排原理,设计合成了14个噁二唑类化合物并评价了它们对黄嘌呤氧化酶的抑制作用,其中5个化合物在10 μmol·L^-1浓度下具有明显的体外酶抑制活性。

Abstract: 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.