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

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.