噁二唑类化合物的设计、合成及黄嘌呤氧化酶抑制活性研究  

Design,synthesis and evaluation of oxadiazoles as novel XO inhibitors

作　　者：王宏占 杨亚军 杨颖 叶菲 田金英 张传明 肖志艳 WANG Hong-zhan;YANG Ya-jun;YANG Ying;YE Fei;TIAN Jin-ying;ZHANG Chuan-ming;XIAO Zhi-yan(School of Pharmacy,Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou 014040;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;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)

机构地区：[1]内蒙古科技大学包头医学院药学院,内蒙古包头014040 [2]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 [3]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

出　　处：《药学学报》2025年第1期164-171,共8页Acta Pharmaceutica Sinica

基　　金：内蒙古自治区自然科学基金项目(2021MS08006);包头医学院博士科研启动基金项目(BYJJ-BSJJ 202007);包头医学院科研创新项目(BYKYCX202415)。

摘　　要：黄嘌呤氧化酶(xanthine oxidase,XO)是高尿酸血症及痛风治疗药物的重要靶点。基于前期获得的高活性XO抑制剂1,采用生物电子等排策略,设计并合成了噁二唑类化合物及其开环类似物共17个。其中,化合物2l、2n、3b在10μmol·L^(-1)浓度下具有显著的XO抑制活性;化合物3b抑制XO的IC50值达到1.45μmol·L^(-1)。Xanthine oxidase(XO)is an important therapeutic target for the treatment of hyperuricemia and gout.Based on the previously identified potent XO inhibitor 1,seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy.Among them,compounds 21,2n,and 3b showed obvious XO inhibitory activity at the concentration of 10μmol-L',and compound 3b exhibited an ICso value of 1.45μmol·L^(-1).

关 键 词：黄嘌呤氧化酶 黄嘌呤氧化酶抑制剂 噁二唑类化合物 高尿酸血症 痛风 

分 类 号：R914[医药卫生—药物化学]