目的 设计并合成一系列奥拉西坦衍生物,并对其促智作用进行研究.方法 以氯乙酰乙酸乙酯为起始原料,通过还原、取代、环合、氨解反应得到目标产物.通过Morris水迷宫测试法测定小鼠的逃避潜伏期以评估小鼠的学习记忆能力.结果 合成了3个目标化合物1～3,其结构经MS、¹H-NMR确证.Morris水迷宫测试表明化合物1～3可明显缩短阿尔茨海默病(AD)小鼠的逃避潜伏期(P<0.01).结论 化合物1～3具有一定的促智活性,对进一步开展奥拉西坦衍生物的结构改造和促智作用研究提供参考.

Objective To design and synthesize a series of oxiracetam derivatives, and to assay their nootropic activities. Methods Chlorine ethylacetoacetate was used as starting material to synthesize the target compounds by reduction, alkylation, condensation, and ammonolysis reactions. To study the nootropic effects of target compounds, the escape latency was used to evaluate the memory ability of mice. Results The target compounds 1—3 were synthesized and characterized by MS and ¹H-NMR. Water maze results showed that compounds 1—3 could shorten the escape latency of AD mice (P< 0.01). Conclusion Compounds 1—3 have the property of improving memory ability of mice, and provide some practical reference value for the further development on the structure modification of oxiracetam derivatives and nootropic activity.

辽宁省教育厅基金资助项目(L2012146)