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

摘要:
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, GABA_R) 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)。

Abstract:
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 ¹H 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 ED₅₀ values ranging from 0.313 7 to 0.360 4 mmol·kg⁻¹.