格列本脲衍生物的设计、合成与降血糖活性  

Design,synthesis and hypoglycemia activity of glibenclamide derivative

作　　者：杜婷婷[1] 陈国良[1] 方武宏 韩尚河[1] 那一凡 刘铮[2] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [2]沈阳药科大学生命科学与生物制药学院药理教研室,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2015年第12期937-940,996,共5页Journal of Shenyang Pharmaceutical University

基　　金：国家基础学科人才培养基金资助项目(J1103606);辽宁省教育厅科研资助项目(L2014378)

摘　　要：目的设计合成格列本脲衍生物并进行降血糖活性研究。方法以5-氯-2-甲氧基苯甲酸为原料,经甲基化、胺解、氯磺化、氮化、缩合反应得到格列本脲二氟衍生物。通过链脲佐菌素(streptozotocin,STZ)配合高脂饲料诱发大鼠Ⅱ型糖尿病模型,评价其降血糖作用。结果经过5步反应合成目标化合物格列本脲二氟衍生物,总收率为28.1%,目标化合物和中间体的结构经1H-NMR和MS确证。活性实验显示格列本脲二氟衍生物具有明显降糖作用。结论在格列本脲的环己烷对位上用2个氟原子取代有利于增加其降血糖活性。Objective To research on design,synthesis and hypoglycemia activity of glibenclamide derivative. Methods The synthesis of 4＇,4＇-difluoroglibenclamide derivative had been accomplished from 5-chloro-2-methoxybenzoic acid,through five steps in 28. 1% overall yield（ based on 5-chloro-2-methoxybenzoic acid）,including methylation,aminolysis,chlorosulfonation,nitrification and condensation reactions. Its hypolycemic effect w as observed in type 2 diabetic rat model induced by high lipid food plus STZ. Results The target structure w as identified by ESI-M S and1H-NM R,and the result of hypoglycemic effect show ed that the difluoroglibenclamide had pow erful hypoglycemic activity. Conclusions It＇s a good strategy to increase hypoglycemic activity by introducing tw o fluorine atoms into glibenclamide.

关 键 词：格列本脲 衍生物 合成 降血糖活性 

分 类 号：R914[医药卫生—药物化学]