α-苄基取代的琥珀酸单酰胺类化合物的设计、合成与生物活性

Design,synthesis and hypoglycemic activity of α-benzylsuccinic acid derivatives

为寻找效果更好的降血糖药物以及进一步研究列奈类化合物的构效关系,以米格列奈为先导物,设计、合成具有降血糖活性的α-苄基取代的琥珀酸单酰胺类化合物。以丁二酸二乙酯和各种取代苯甲醛为原料,经缩合、水解得苯亚甲基丁二酸,再进行酸酐化、胺解和氢化等反应合成了12个目标化合物,化合物结构通过元素分析、IR、1HNMR和ESI-MS得以确证,并测定了它们的降血糖活性。初步药理试验表明所合成的化合物中6c、6e和6g降糖作用较明显,其中6e较为突出,其降糖作用与那格列奈相当。

Based on the SAR of glinide agents, mitiglinide has been modified to study the SAR of glinides. α-Benzylsuccinic acid derivatives which were designed and synthesized in order to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds. From ethyl succinate and substituded benzaldehydes, twelve new target compounds were synthesized by codensation, hydrolysis, anhydridization, amidation and hydrogenization reactions, and their hypoglycemic activity were evaluated with glucose oxidase kit. All the compounds were characterized by elemental analysis, IR, ^1H NMR and ESI-MS. The preliminary pharmacological test showed that the compounds have good hypoglycemic activity, especially 6c, 6c and 6g, 6e showed the same hypoglycemic potency as nateglinide.