呋喃丙烯酰基哌嗪类化合物的合成及其对血清诱导的血管平滑肌细胞的抑制活性

Synthesis and inhibitory activities on vascular smooth muscle cell proliferation of furan-acrylic acyl group piperazine derivatives

目的设计合成9种呋喃丙烯酰基哌嗪类化合物,测试其生物活性。方法根据药物拼合原理,采用文献的步骤,先合成了呋喃丙烯酸,然后以此为原料分别与9种不同的取代苄基哌嗪进行反应,得到目标化合物。并对其进行了血清诱导的血管平滑肌细胞增殖的抑制活性检测,在活性实验中,取用了不同的药物浓度,并与空白试验进行对照,使用MTT法来检测细胞的增殖情况。结果成功合成了9个目标化合物,所用方法条件温和,产率较高,所有化合物的结构均经红外光谱、核磁共振氢谱、元素分析和质谱等手段表征。初步活性测试结果表明,所合成的产物在不同浓度下,均表现出一定的抑制活性,浓度为15μg/mL所合成化合物抑制率均最高。其中化合物3e,3f,3 g各浓度的抑制活性明显高于其他化合物,值得进行进一步的药理研究。结论本研究为哌嗪类化合物的合成找到了一种新的方法,同时也发现了其对血管平滑肌细胞增殖有抑制作用。

Objective To synthesis,nine N-[3-（2-furanyl）-acryloyl]-N＇-substituted benzyl piperazine derivatives were synthesized and evaluated for their primary biological activities.Methods First,the furylacrylic acid was synthesized,Then the target compounds could be obtained by direct furylacrylic acid with the different substituted benzyl piperazine derivatives.In the biological active experiments,taking the different concentrations,comparing with the blank test,the inhibitory effect of the target compounds on VSMC proliferation was investigated by MTT.Results The successful synthesis of nine new compounds.The method was mild and get high yields.The structures of these compounds were confirmed by IR1H-NMR,MS,and elemental analysis.The results of preliminary activity test showed that the synthesized products exhibited inhibitory activity at different concentrations,and the highest inhibitory rate was 15 μg/mL.Pharmacological results showed that the compounds 3e,3f and 3 g showed the moderate inhibitory activities against vascular smooth muscle cells proliferation were higher than other compounds,and were worth further studying.Conclusion The synthesized compounds have inhibitory activities and could very well lead to the development of novel types of treat atherosclerosis drug.