五环三萜含氮衍生物的合成及糖原磷酸化酶抑制活性  

Synthesis and biological evaluation of novel amide derivatives of pentacyclic triterterpenes as inhibitors of glycogen phosphorylase

作　　者：李晶[1] 靳晓婷[1] 张丽颖[1] 

机构地区：[1]承德医学院中药研究所,河北省中药研究与开发重点实验室,承德067000

出　　处：《中国药科大学学报》2016年第4期422-428,共7页Journal of China Pharmaceutical University

基　　金：河北省高等学校研究优秀青年基金资助项目(No.Y2012026)~~

摘　　要：以五环三萜化合物科罗索酸为原料,经乙酰化保护、酰胺化、水解等反应,合成了8个科罗索酸C-28位酰胺衍生物;以齐墩果酸为原料,经酰化、烷基化、催化氢化等反应合成了6个齐墩果酸C-3位含氮衍生物,所有目标化合物进行了糖原磷酸化酶抑制活性测试。结果表明:11个化合物表现出不同程度的抑酶活性,其中4个化合物活性强于其先导化合物,其中目标化合物6的糖原磷酸化酶抑制活性最强,IC50为11.2μmol/L。Eight novel amide derivatives of corosolic acid were synthesized by acylation, amidation and hydrolysis reactions, etc. Six novel amide derivatives of oleanolic acid were synthesized by acylation, alkylation and reduction reactions, etc. Biological evaluation of the target compounds as inhibitors of glycogen phosphorylase （GP） has been described. Results indicated that eleven derivatives exhibited moderate-to-good inhibitory activities against glycogen phosphorylase. Among them, four target compounds possess better inhibition effects than lead compounds and compound 6 show the best inhibition effect with the IC50 of 11.2 μmol/L.

关 键 词：五环三萜 科罗索酸 齐墩果酸 糖原磷酸化酶抑制剂 合成 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]