【摘要】 目的:通过研究五环三萜类新型糖原磷酸化酶抑制剂的构效关系,发现新型降血糖药物。方法:以熊果酸为先导化合物,对其进行结构修饰和抑制兔肌肉糖原磷酸化酶活性的测试。结果:共合成15个熊果酸衍生物,其结构经IR、1H NMR、MS和元素分析确证;生物活性测试显示:熊果酸(IC50=9μmol/L)是一个中等强度的糖原磷酸化酶抑制剂,大部分合成衍生物都显示出一定的抑制糖原磷酸化酶的活性。结论:抑制肝糖原降解是熊果酸的降血糖作用机制之一,对熊果酸C-28位的结构改造值得进一步研究。更多还原

【Abstract】 Aim:To study the structure-activity relationships of ursolic acid derivatives as a new class of glycogen phosphorylase inhibitors and to search for novel anti-diabetic drugs.Methods:Structural modifications were performed with ursolic acid as a lead compound.Results:Fifteen compounds were synthesized and their structures were confirmed by IR,（）¹H NMR,MS and elemental analysis.The assay results showed that ursolic acid(IC₅₀=9 μmol/L)is a mild inhibitor of glycogen phosphorylase and most of the synthesized compounds exhibited inhibitory activity against rabbit muscle GPa.Conclusion:It is proposed that ursolic acid might reduce blood glucose,at least in part,through inhibiting hepatic glycogen degradation.Modifications at C-28 of ursolic acid deserve further study.更多还原