4-(2-乙酰氧基苯甲酰氨基) 丁酸酯类化合物的设计、合成及抗癫痫活性研究

Design, synthesis and antiepileptic activity of 4-(2-acetoxybenzoylamino) butyrate derivatives

摘要:
以中枢抑制性神经递质γ-氨基丁酸 (GABA) 受体调节位点为靶点, 以GABA (1) 为原料设计合成了12个未见文献报道的4-(2-乙酰氧基苯甲酰氨基) 丁酸及酯类化合物 (7a～7k)。目标化合物经IR、¹H MNR、EI-MS及元素分析确证了结构。初步体外活性表明, 所合成的化合物具有不同程度的抗癫痫活性, 其中化合物7i～7k具有很好的抗癫痫活性, 值得进一步研究, 化合物4、7d～7h显示较好的抗癫痫活性。在此基础上, 初步讨论了该类化合物的构效关系。

Abstract:
A series of 4-(2-acetoxybenzoylamino) butyrate derivatives were designed and synthesized. All of the novel 12 compounds (7a−7k) were synthesized from γ-aminobutyric acid (1) as starting material, and their structures were confirmed with IR, ¹H NMR, EI-MS and elemental analysis. Preliminary pharmacological test in vitro showed that most of these title compounds possessed antiepileptic activity. Compounds 7i−7k displayed strong antiepileptic activity and are worth for further development. Compounds 4, 7d−7h showed moderate antiepileptic activity. The structure-activity relationship of 4-(2-acetoxybenzoylamino) butyrate derivatives is also discussed preliminarily.