药学学报, 2016, 51(6): 954-960
引用本文:
严定安, 张蕾, 田金英, 叶菲, 肖志艳. 噁二唑类黄嘌呤氧化酶抑制剂的设计合成及活性评价[J]. 药学学报, 2016, 51(6): 954-960.
YAN Ding-an, ZHANG Lei, TIAN Jin-ying, YE Fei, XIAO Zhi-yan. Design, synthesis and biological evaluation of oxadiazole derivatives as xanthine oxidase inhibitors[J]. Acta Pharmaceutica Sinica, 2016, 51(6): 954-960.

噁二唑类黄嘌呤氧化酶抑制剂的设计合成及活性评价
严定安1, 张蕾1, 田金英2, 叶菲2, 肖志艳1
1. 中国医学科学院、北京协和医学院药物研究所, 活性物质发现与适药化研究北京市重点实验室, 北京 100050;
2. 中国医学科学院、北京协和医学院药物研究所, 新药作用机制研究与药效评价北京市重点实验室, 北京 100050
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。
关键词:    黄嘌呤氧化酶      高尿酸血症      噁二唑衍生物     
Design, synthesis and biological evaluation of oxadiazole derivatives as xanthine oxidase inhibitors
YAN Ding-an1, ZHANG Lei1, TIAN Jin-ying2, YE Fei2, XIAO Zhi-yan1
1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China;
2. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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.
Key words:    xanthine oxidase    hyperuricemia    oxadiazole derivative   
收稿日期: 2016-03-25
DOI: 10.16438/j.0513-4870.2016-0278
基金项目: 国家"重大新药创制"科技重大专项"十二五"综合平台项目(2012ZX09301002001004).
通讯作者: 肖志艳,Tel/Fax:86-10-63189228,E-mail:xiaoz@imm.ac.cn
Email: xiaoz@imm.ac.cn
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