目的 設(shè)計(jì)并合成一系列奧拉西坦衍生物,并對(duì)其促智作用進(jìn)行研究.方法 以氯乙酰乙酸乙酯為起始原料,通過還原、取代、環(huán)合、氨解反應(yīng)得到目標(biāo)產(chǎn)物.通過Morris水迷宮測(cè)試法測(cè)定小鼠的逃避潛伏期以評(píng)估小鼠的學(xué)習(xí)記憶能力.結(jié)果 合成了3個(gè)目標(biāo)化合物1～3,其結(jié)構(gòu)經(jīng)MS、¹H-NMR確證.Morris水迷宮測(cè)試表明化合物1～3可明顯縮短阿爾茨海默病(AD)小鼠的逃避潛伏期(P<0.01).結(jié)論 化合物1～3具有一定的促智活性,對(duì)進(jìn)一步開展奧拉西坦衍生物的結(jié)構(gòu)改造和促智作用研究提供參考.

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.

遼寧省教育廳基金資助項(xiàng)目(L2012146)