Abstract

Prodrugs of metformin were synthesized with the goal of enhancing biological activity of metformin. They were synthesized by combining metformin with 2-substituted indolizine (C7–C12). The synthesized prodrugs were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy. The chemical hydrolysis of C7–C12 was carried out at pH 1.2, 6.8, and 7.4. All compounds showed encouraging chemical stability at pH 1.2 and 6.8, whereas mild hydrolysis was shown at pH 7.4. Further prodrugs were screened for antidiabetic activity using a streptozotocin-induced model in rat. These derivatives showed notable results. Among them C8 showed significant activity in the reduction of STZ-induced blood glucose in rats when compared to that of metformin, indicating the effectiveness of prodrug.

摘要

合成二甲双胍的前药以增强二甲双胍的生物活性。它们是通过将二甲双胍与 2-取代的中氮茚 ( C7–C12 ) 组合而成的。合成的前药通过IR、¹ H NMR、¹³ C NMR和质谱进行表征。C7-C12的化学水解在 pH 1.2、6.8 和 7.4 下进行。所有化合物在 pH 1.2 和 6.8 时都表现出令人鼓舞的化学稳定性，而在 pH 7.4 时则表现出温和的水解。使用链脲佐菌素诱导的大鼠模型筛选其他前药的抗糖尿病活性。这些衍生物显示出显着的结果。其中C8与二甲双胍相比，在降低 STZ 诱导的大鼠血糖方面显示出显着的活性，表明前药的有效性。