苄基哌嗪类衍生物的合成与蛋白酪氨酸激酶抑制活性的研究

Synthesis and protein tyrosine kinases inhibitory activity of substituted benzyl piperazine derivatives

目的合成苄基哌嗪类衍生物,考察目标化合物对蛋白酪氨酸激酶(PTK)的抑制活性。方法用呋喃甲醛和丙二酸合成呋喃丙烯酸,以15种取代苄基哌嗪为原料,分别与呋喃丙烯酸反应得到目标化合物。采用酶联免疫吸附法(Elisa)测定所得化合物对PTK的抑制活性,并计算抑制率,筛选出具有抑制PTK活性的化合物。结果所得化合物均对PTK有一定的抑制活性。结论通过优化反应条件,成功合成15种苄基哌嗪类化合物,原料廉价易得,合成方法简单,反应温和。化合物结构经IR、1HNMR、EA和MS确证。经初步活性筛选发现化合物2h和2k的抑制活性较强。

Objective Substituted benzyl piperazine derivatives were designed,synthesized and screened for their protein tyrosine kinases(PTK)inhibitory activity.Methods First,furylacrylic acid was synthesized from furan formaldehyde and malonic acid.Fifteen substituted benzyl piperazine were then used as the raw material to synthesize the new piperazine derivatives.Enzyme-linked immunosorbent assay(Elisa)was used for caculating the inhibition rate,which was used to evaluate the compounds with PTK inhibitory activity.Results All of the target derivatives exhibited good inhibitory activity against PTK.Conclusion By optimizing the reaction conditions,15 new compounds were synthesized.The synthetic method is simple,and the materials are cheap and readily available,and their structures were verified by IR,1H NMR,MS and elemental analysis.Preliminary activity screening test showed that compounds 2h and 2k had the strong inhibitory activity.