米格列奈类似物的合成及其降血糖作用

Synthesis and Hypoglycemic Activity of Mitiglinide Analogues

目的:研究米格列奈类似物的合成及其降血糖作用。方法:由丁二酸二甲酯经缩合、水解、酸酐化、胺解、氢化和成盐等反应合成目标物;测定目标物的降血糖效果。结果:合成了13个新的中间体和13个新目标化合物,其结构经IR,1H NMR和ESI-MS质谱确证。结论:初步降血糖活性测试表明,目标化合物XL 03、XL06、XL 08和XLH 01对正常小鼠有明显的降血糖活性,其中化合物XL 06降低血糖的作用与米格列奈相当。

AIM ： To study the synthesis and hypoglycemic activity of mitiglinide analogues. METHODS ： The target compounds were synthesized from dimethyl succinate v/a condensation, hydrolysis, anhydridization, amidation, hydrogenization and salification reactions. The hypoglycemic activities of target compounds were evaluated. RESULTS： Thirteen new intermediates and thirteen new target compounds, which were never reported, were synthesized. Structures of all the compounds were conffirmed by IR, ^1 H NMR and ESI-MS. CONCLUSION： The pharmacological study showed that four new mitiglinide analogues （XL 03, XL 06, XL 08 and XLH 01） exhibited considerable hypoglycemic activity. XL 06 showed the same hypoglycemic potency as mitiglinide