URAT1抑制剂研究进展及药物化学策略  

Research progress and medicinal chemistry strategies of URAT1 inhibitors

作　　者：史晓雨 赵彤 章健 梁瑞鹏 张志姣 刘新泳[1] 展鹏[1] SHI Xiao-yu;ZHAO Tong;ZHANG Jian;LIANG Rui-peng;ZHANG Zhi-jiao;LIU Xin-yong;ZHAN Peng(Key laboratory of Chemical Biology(Ministry of Education),Department of Medicinal Chemistry,School of Pharmaceutical Sciences,Shandong University,Jinan 250012,China)

机构地区：[1]山东大学药学院药物化学研究所,化学生物学教育部重点实验室,山东济南250012

出　　处：《药学学报》2022年第10期2960-2971,共12页Acta Pharmaceutica Sinica

基　　金：山东省重大科技创新工程项目(2019JZZY021011)。

摘　　要：尿酸转运蛋白1(URAT1)是一种位于人肾近曲小管上皮细胞顶膜的阴离子膜转运蛋白,控制尿液中尿酸盐的重吸收。临床发现约90%的痛风及高尿酸血症患者表现出明显的尿酸排泄不足。因此,开发能够通过增强肾脏尿酸盐排泄来降低体内血尿酸水平的URAT1抑制剂是抗痛风药物近年的研发热点。本文综述了具有降尿酸或抗痛风药理作用的URAT1抑制剂及其药物化学策略,以期为新型抗痛风及高尿酸血症药物的研发提供参考。The urate transporter 1(URAT1)which controls urate reabsorption is a membrane transporter in the apical membrane of human renal proximal tubule epithelial cells.It was found that about 90%of patients suffer from hyperuricemia due to insufficient uric acid excretion.Therefore,the development of URAT1 inhibitors that can reduce the level of serum uric acid in vivo by enhancing renal urate excretion has been a hot spot in seeking anti-gout drugs in recent years.In this article,the representative URAT1 inhibitors with uric acid-lowering or antigout effects are reviewed,and related medicinal chemical strategies are analyzed,hoping to provide valuable insights into the discovery of new URAT1 inhibitors.

关 键 词：尿酸 高尿酸血症 痛风 雷西纳德 URAT1抑制剂 

分 类 号：R914[医药卫生—药物化学]