2-[1-(2-吡啶)乙氧基]乙酸2-[4-苄基取代哌嗪]乙酯的合成及对小鼠学习记忆的促进作用

[目的]合成2-[1-(2-吡啶)乙氧基]乙酸2-[4-苄基取代哌嗪]乙酯类化合物,探讨其对小鼠学习记忆能力的影响.[方法]使用2-乙基吡啶为起始原料,经Whol-ziegler反应得到2-(1-溴乙基)吡啶,再与羟基乙酸乙酯的醇钠盐缩合得到2-[1-(2-吡啶)乙氧基]乙酸乙酯.无水哌嗪与不同取代的氯苄反应分别得到化合物4a～4l.化合物4a～4l分别与溴乙醇反应得到化合物5a～5l.化合物2-[1-(2-吡啶)乙氧基]乙酸乙酯与化合物5a～5l经酯交换反应得到目标化合物6a～6l.采用通道式水迷宫法测定化合物6j的促进小鼠学习记忆活性.[结果]设计合成了12个尚未见文献报道的新化合物,结构经核磁共振谱、红外光谱等确证.与模型对照组比较,化合物6j大、小剂量组到达时间显著缩短,错误次数明显减少,相比较差异均有统计学意义(P<0.05).[结论]化合物6j具有良好的促进小鼠学习记忆作用.

Synthesis and effects of 2-(4-(4-benzyl-substituted)piperazin-1-yl)ethyl 2-(1-(py-ridin-2-yl)ethoxy) acetates on learning and memory facilitation in mice

OBJECTIVE To synthesize the 2-(4-(4-benzyl-substituted) piperazin-1-yl) ethyl 2-(1-(pyridin-2-yl) ethoxy) acetates,and to study the its effects on learning and memory facilitation in mice.METHODS The 2-(1-bromoethyl) pynidine(2) was obtained through Whol-ziegler reaction by using 2-ethylpyridine(1) as the starting material,and the compound 2 was reacted with sodium 2-ethoxy-2-oxo-ethanolate to give ethyl [2-(1-(pyridine-2-yl)ethoxy)] acetate(3).The compounds 4a-4l were obtained by the reaction of piperazine anhydrous with different benzyl chlorides,and the compounds 4a-4l and bromoethanol were used to synthesize compounds 5a-5l,and they were further reacted with compound 3 to obtain compounds 6a-6l,respectively.The effects of compound 6j on learning and memory in mice were tested by using water maze test.RESULTS Twelve new compounds were designed and synthesized,and the structures of compounds were confirmed by IR,1H-NMR and MS spectrum.As compared with the model control group,the arriving times significantly shortened,and the numbers of errors obviously diminished in large and small doses of compound 6j groups(P<0.05).CONCLUSION The pharmacological results showed that compound 6j has strong learning and memory facilitation in mice.