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

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...