苯甲酰胺类sEH抑制剂的设计、合成及活性研究  

Design,synthesis and activity evaluation of benzamides as sEH inhibitors

作　　者：朱艳丽 韩宇[1] 赵建国 魏家宽 李元 赵燕芳[1] 侯云雷 宫平[1] ZHU Yanli;HAN Yu;ZHAO Jianguo;WEI Jiakuan;LI Yuan;ZHAO Yanfang;HOU Yunlei;GONG Ping(School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2024年第5期351-360,共10页Chinese Journal of Medicinal Chemistry

基　　金：沈阳药科大学创新创业训练计划项目(202210163026)。

摘　　要：目的设计合成一系列新型苯甲酰胺类sEH抑制剂,测定其对sEH的体外抑制活性,初步总结该类化合物的构效关系,为后期研究提供参考。方法以课题组前期发现的苯甲酰胺类sEH抑制剂A34为先导化合物,通过生物电子等排等策略,设计并合成新型苯甲酰胺类sEH抑制剂;以A34为阳性对照,采用Cayman荧光法测定目标化合物对sEH的体外抑制活性。结果与结论设计并合成了7个苯甲酰胺类化合物X-1~X-7,其结构均经MS和^(1)H-NMR谱确证。活性测试结果表明,化合物X-4具有较高的sEH抑制活性,IC_(50)值为0.1 nmol·L^(-1),可作为优选化合物进行深入研究。In order to discover new anti-inflammatory compounds and improve the metabolic stability and solubility of A34 with good inhibitory activities on sEH,seven compounds(X-1-X-7)were designed and synthesized using compound A34 as the lead compound.The structures of the target compounds were confirmed by MS and ^(1)H-NMR.With A34 as the positive control drug,all the target compounds were evaluated in vitro for inhibitory by Cayman fluorescence method.The results showed that most of target compounds showed varying degrees of inhibitory activities on sEH.Compound X-4 exhibited better inhibitory activity with IC_(50)value of 0.1 nmol·L^(-1)compared with the positive control drug,and it could be developed for further research.

关 键 词：sEH抑制剂 苯甲酰胺类 构效关系 设计与合成 

分 类 号：R914[医药卫生—药物化学]