取代苄基哌嗪类化合物的合成及其蛋白酪氨酸激酶抑制活性的研究

摘要

目的 以取代苄基哌嗪为基本原料,设计合成具有蛋白酪氨酸激酶(PTK)抑制活性的哌嗪类化合物.方法 以苯甲酸为初始化合物,合成中间体苯甲酸(2-氯)乙酯,将中间体分别与15种取代苄基哌嗪进行反应,合成目标化合物.采用酶联免疫吸附法(ELISA)测定PTK抑制活性并计算抑制率,筛选出具有抑制PTK活性的化合物.结果 合成苄基哌嗪类化合物15个,结构经IR、1H NMR、MS和元素分析进行确证.经初步筛选表明化合物3h、3o的PTK抑制活性较高.结论 目标化合物合成方法简单,反应温和,原料易得廉价.化合物3h、3o的PTK抑制活性较强.%Objective Using substituted benzyl piperazine as the raw material to design and synthesize new piperazine deriva-tives with protein tyrosine kinase(PTK)inhibitory activity. Methods Benzoic acid was used as starting compound to synthesize a key intermediate,2-chloroethyl benzoate,and the target compounds were synthesized by further reaction of the key intermediate with different substituted benzyl piperazine derivatives.Enzyme-linked immunosorbent assay(ELISA)was used to test the PTK inhibitory activity of the compounds.Results Fifteen new compounds were synthesized and their structures were verified by IR,1H NMR,MS, and elemental analysis.The PTK inhibitory activity of 3h and 3o was stronger than that of the other compounds.Conclusion The syn-thetic method is simple,and the raw materials are cheap and readily available.Compounds 3h and 3o showed relatively higher PTK in-hibitory activities.