甲磺酸加贝酯衍生物的合成及其对蛋白酶活性的抑制  

Synthesis of Gabeyl Mesylate Derivatives for Protease Inhibition

作　　者：孙正扬 闫旭冉 姜军 王凯[1] SUN Zhengyang;YAN Xuran;JIANG Jun;WANG Kai(College of Health Science and Engineering,Hubei University,Wuhan 430062,China)

机构地区：[1]湖北大学健康科学与工程学院,湖北武汉430062

出　　处：《武汉工程大学学报》2023年第4期395-400,455,共7页Journal of Wuhan Institute of Technology

基　　金：湖北省功能化学品工程技术研究中心开放课题(GCZX-2022-01)。

摘　　要：通过生物电子等排原理,以6-胍基己酸盐酸盐为起始原料,与含有酚羟基的不同取代苯甲酸乙酯,经过缩合和酸化反应,设计和合成了甲磺酸加贝酯及其衍生物。同时,考察了这些衍生物与胰蛋白酶相互作用,对胰蛋白酶抑制剂活性进行了初步评价,其TIA值为0.93~1.23 mg/g之间。结果表明:结构中的胍基和酯基对于抑制蛋白酶的活性至关重要,为后续的甲磺酸加贝酯类药物研究提供改造思路,奠定初步工作基础。Applying bioisosterism principles and using 6-guanidinohexanoic acid hydrochloride as a starting material,gabexate mesylate and its derivatives were designed and synthesized through condensation and acidification reactions with different substituted ethyl benzoates including phenolic hydroxyl group.At the same time,the interaction between these derivatives and trypsin was investigated,and the activity of trypsin inhibitor was preliminarily evaluated,with their trypsin inhibiting activity values of 0.93-1.23 mg/g.The results showed that the guanidine and ester groups in their structure should be crucial for inhibiting the trypsin activity,which provides a modification approach for subsequent research on gabexate mesylate drugs and lays a preliminary work foundation.

关 键 词：甲磺酸加贝酯衍生物 生物电子等排体 蛋白酶活性抑制剂 合成 

分 类 号：O626.13[理学—有机化学]