杂环并五环三萜化合物的合成及糖原磷酸化酶抑制活性  

Synthesis and biological activity of heterocycle-fused derivatives of pentacylic triterpenes as glycogen phosphorylase inhibitors

作　　者：温小安[1] 张迎霞[1] 柳军[2] 张陆勇[2] 倪沛洲[3] 孙宏斌[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009 [2]中国药科大学新药筛选中心,南京210009 [3]中国药科大学有机化学教研室,南京210009

出　　处：《中国药科大学学报》2009年第6期491-496,共6页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.30672523,No.90713037)~~

摘　　要：目的:对天然五环三萜进行结构修饰,寻找新型糖原代谢调控药物。方法:以齐墩果酸和熊果酸为先导物,在其A环骈合吲哚环、喹喔啉环和吡嗪环,合成一系列含氮杂环衍生物,并采用兔肌肉糖原磷酸化酶筛选模型评价其活性。结果与结论:合成了12个杂环衍生物,结构均经IR、1H NMR、13C NMR和MS确证。除化合物12外,其余化合物均显现出糖原磷酸化酶抑制活性,IC50在14～252μmol/L范围内。其中,化合物15活性最好,其IC50为14μmol/L。Aim:To search for novel modulators of glycogen metabolism through structural modifications of natural pentacyclic triterpenes.Methods:A series of N-heterocyclic derivatives were synthesized by fusing indole,quinoxaline and pyrazine rings with A-ring of oleanolic and ursolic acids.The compounds were biologically evaluated for their inhibitory activity against rabbit muscle glycogen phosphorylase.Results and Conclusion:Twelve heterocyclic triterpene derivatives were synthesized and their structures were confi...

关 键 词：五环三萜 结构修饰 杂环化合物 糖原磷酸化酶抑制剂 

分 类 号：R284.1[医药卫生—中药学]