4-(2-乙酰氧基苯甲酰氨基)丁酰胺基杂环化合物的合成及活性研究

Synthesis and activities of 4-(2-acetoxybenzoylamino) butyramide heterocyclic compounds

前期研究发现,4-(2-乙酰氧基苯甲酰氨基)丁酰胺类化合物具有较好的抗癫痫活性。据此,本文以中枢γ-氨基丁酸受体(γ-aminobutyric acid receptor,GABAR)为靶点,设计合成了系列全新结构的4-(2-乙酰氧基苯甲酰氨基)丁酰胺基杂环类化合物(5a～5n),希望完善此类化合物的构效关系及提高其抗癫痫活性。化合物结构经1H MNR、ESI-MS及元素分析确证。体内药效筛选结果表明,化合物5f、5i～5n对4-AP致癫痫小鼠具有良好抗癫痫活性(ED50值为0.313 7～0.360 4 mmol.kg 1)。

It has been demonstrated by our previous research that 4-（2-acetoxybenzoylamino） butyramide derivatives exhibited good antiepileptic activities. In this paper, to explore the SAR and improve the antiepileptic activities of these derivatives, a series of novel 4-（2-acetoxybenzoylamino） butyramide heterocyclic compounds （5a-5n） were synthesized and biologically evaluated. Their structures were confirmed by IH MNR, ESI-MS and elemental analysis. Pharmacological test in vivo showed that target compounds （5f, 5i-5n） displayed strong antiepileptic activities on 4-AP induced epilepsy in mice with EDso values ranging from 0.313 7 to 0.360 4 mmol.kg-1.