噻唑联苯并呋喃衍生物的设计、合成及活性研究  

Design,Synthesis and Activity Study of Thiazole Linking Benzofuran Derivatives

作　　者：谢珺 苗菁 崔杏 王建塔 王聪 汤磊 XIE Jun;MIAO Jing;CUI Xing;WANG Jian-ta;WANG Cong;TANG Lei(College of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学药学院,贵州贵阳550004 [2]贵州医科大学贵州省化学合成药物研发利用工程技术研究中心,贵州贵阳550004

出　　处：《化学试剂》2022年第12期1843-1848,共6页Chemical Reagents

基　　金：贵州省卫生健康委科学技术基金资助项目(gzwkj2023-232);化学药仿创技术应用国家地方联合工程技术研究中心资助项目(2019);贵州省常见重大慢性疾病发病机制及药物开发应用创新基地资助项目(黔科中引地[2021]4029)。

摘　　要：黄嘌呤氧化酶是治疗高尿酸血症、痛风等相关疾病的重要靶点。通过对非布索坦的构效关系的分析,并基于药物化学的拼合原理,将非布索坦的噻唑环和苯溴马隆的苯并呋喃环拼合,设计合成了12个化合物,结构经过^(1)HNMR、^(13)CNMR和HRMS鉴定。对目标化合物进行黄嘌呤氧化酶的活性测试,2-(2-乙基-5-氟苯并呋喃-3-乙基)-4-甲基-5-噻唑甲酸具有相对较好的活性。分子对接的结果说明2-(2-乙基-5-氟苯并呋喃-3-乙基)-4-甲基-5-噻唑甲酸与黄嘌呤氧化酶的相互作用和非布索坦相似。该化合物结构可以进步优化,为黄嘌呤氧化酶抑制剂的提供候选化合物。Xanthine oxidase is an important target for the treatment of hyperuricemia,gout,and other related diseases.Based on the analysis of the structure-activity relationship of febuxostat and the principle of pharmaceutical chemistry,12 compounds were designed and synthesized by combining the thiazole ring of febuxostat with the benzofuran ring of benbromarone,and their structures were identified by ^(1)HNMR,^(13)CNMR and HRMS spectra.Moreover,the xanthine oxidase activities of the target compounds were tested,and the results showed that 2-(2-ethyl-5-fluorobenzofuran-3-ethyl)-4-methyl-5-thiazole carboxylic acid had the good activity.Molecular docking results revealed that the interaction between 2-(2-ethyl-5-fluorobenzofuran-3-ethyl)-4-methyl-5-thiazole carboxylic acid and xanthine oxidase was similar to febuxostat.In future,this structure can be further optimized as an candidate for xanthine oxidase inhibitor.

关 键 词：非布索坦 黄嘌呤氧化酶抑制剂 痛风 设计 生物活性 

分 类 号：R914.5[医药卫生—药物化学]