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
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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.
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