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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

  • 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14~252 μmol/L范围内。其中,化合物 15 活性最好,其IC50为14 μmol/L。

     

    Abstract: 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 confirmed by IR,1H NMR,13C NMR and MS.Except for compound 12 ,all of the compounds exhibited glycogen phosphorylase inhibitory activity with IC50 values in the range of 14-252 μmol/L.Among this series of compounds,compound 15 showed the best potency with IC50 of 14 μmol/L.