酰胺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 amide derivatives as xanthine oxidase inhibitors

黄嘌呤氧化酶(xanthine oxidase,XO)是尿酸代谢中的关键酶,其抑制剂在降尿酸治疗中发挥着重要的作用。本文以非布索坦(febuxostat)和托匹司他(topiroxostat)为模板,设计合成了18个酰胺类化合物,其中6个化合物在10μmol·L^(-1)浓度下显示出一定的黄嘌呤氧化酶抑制活性。分子对接研究初步阐明了此类化合物的作用模式,为后续结构优化提供了依据。

Xanthine oxidase （XO） is a key enzyme in play an important role in the antihyperuricemic therapy. the synthesis of uric acid. Therefore, XO inhibitors Based on the template structures of febuxostat and topiroxostat, 18 amide derivatives were designed and synthesized. Among them, six showed apparent inhibitory activity against XO under the concentration of 10 μmol.L-1. Molecular docking revealed the possible interaction mode of this compound class, which may provide a clue for further molecular design.