基于Click反应设计和合成新型HDAC抑制剂  

Design and Synthesis of Novel HDAC Inhibitors Based on Click Reaction

作　　者：朱明霞 张蓬勃 宋艳玲 ZHU Mingxia;ZHANG Pengbo;SONG Yanling(Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]沈阳化工大学制药与生物工程学院,辽宁沈阳110142

出　　处：《沈阳化工大学学报》2024年第3期233-237,共5页Journal of Shenyang University of Chemical Technology

基　　金：辽宁省教育厅科技计划一般项目(LJ2020025)。

摘　　要：利用Click反应将活性片段进行拼接,设计并合成新型的抗肿瘤药物组蛋白去乙酰化酶(histone deacetylase,HDAC)抑制剂.以3-氟邻苯二甲酸酐为起始原料,通过取代反应得到3-丙炔氨基邻苯二甲酸酐(化合物1);以2-溴乙醇为起始原料通过Williamson反应、对甲苯磺酰化反应和叠氮化反应得到化合物4a—4c;化合物1和化合物4a—4c通过Click反应得到目标化合物5a—5c.目标化合物结构经1H-NMR进行确认,并采用HDACs试剂盒对目标化合物进行活性测试.初步生物活性测试结果表明化合物5b与阳性对照药物具有相当的HDAC抑制活性.Histone deacetylase(HDAC)inhibitor is a new antitumor drug.In this paper,two active fragments were spliced by Click reaction to design and synthesize a new HDAC inhibitor.Compound 1 was prepared from 3-fluorophthalic anhydride by substitution reaction.Compound 4a—4c was obtained by Williamson reaction,p-toluenesulfonylation and azide reaction with 2-bromoethanol.Compound 5a—5c were obtained by Click reaction with Compound 1 and 4a—4c.The structures of the target compounds were confirmed by 1H-NMR,and the activity of the target compounds were tested by HDACs kit.The preliminary biological activity test showed that compound 5b had the same HDAC inhibitory activity as the positive control drug.

关 键 词：HDAC抑制剂 CLICK反应 设计 合成 

分 类 号：R978.1[医药卫生—药品]