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 Inhibitor

作　　者：何雄 张春盛 曾灿丽 贺莲 张静 杨世平 He Xiong;Zhang Chunsheng;Zeng Canli;He Lian;Zhang Jing;Yang Shiping(KAMP Pharmaceutical Co.,Ltd.,Changsha 410013,China)

机构地区：[1]康普药业股份有限公司,湖南长沙410013

出　　处：《广东化工》2020年第8期38-40,29,共4页Guangdong Chemical Industry

摘　　要：目的黄嘌呤氧化酶(XOD)抑制剂对痛风或其他由于XOD诱导的疾病有潜在的治疗作用,本文设计合成了一系列噁二唑类衍生物,并对其黄嘌呤氧化酶的抑制活性进行初步的评价。方法:以4-氰基苯肼为原料,经缩合、环合、肼解、烃化等化学反应合成目标产物。以非布索坦为阳性对照,用牛源的黄嘌呤氧化酶对所合成的化合物进行体外抑制活性的评价。结果:合成了13个化合物,其中4个化合物未见相关文献报道,其结构经核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)和高分辨质谱(HRMS)等确征。对设计、合成的13个噁二唑类化合物进行了黄嘌呤氧化酶的抑制作用的评价,其中8个化合物在10μmol·L-1浓度下具有明显的体外黄嘌呤氧化酶抑制活性。OBJECTIVE Xanthine oxidase(XOD)inhibitors have potential therapeutic effects on gout or other diseases induced by XOD.In this paper,a series of oxadiazole derivatives were designed and synthesized,and the inhibitory activity of XOD was evaluated.METHODS:The target product was synthesized from 4-cyanophenylhydrazine by condensation,cyclization,hydrazinolysis and alkylation.With febuxostat as the positive control,the inhibitory activity of the synthesized compound was evaluated in vitro with cattle xanthine oxidase.RESULTS:Thirteen compounds have been synthesized,four of which have not been reported in literature.Their structures have been confirmed by1H NMR,13C NMR and HRMS.The inhibitory effect of xanthine oxidase on 13 oxadiazole compounds was evaluated.Among them,8 compounds had obvious inhibitory activity of xanthine oxidase in vitro at the concentration of 10μmol·L-1.

关 键 词：噁二唑衍生物 黄嘌呤氧化酶 合成 活性 

分 类 号：R977.7[医药卫生—药品]