目的设计并合成高抑制活性的小分子Bcl-2蛋白抑制剂。方法基于已报道的活性小分子,运用Autodock 4.2软件研究其与Bcl-2蛋白的作用模式,探索Bcl-2蛋白的关键位点并设计、合成一系列新型小分子抑制剂,并进行体外抗肿瘤活性的实验。结果设计合成了8个全新的小分子化合物,其结构经1HNMR和13CNMR确证。结论所合成的8个化合物均有明显的体外抗肿瘤活性,且大部分高于阳性对照紫杉醇。 Objective To design and synthesize a small molecule Bcl-2 protein inhibitor with high inhibitory activity. Methods Based on the reported small active molecules, Autodock 4.2 software was used to study the interaction between Bcl-2 and Bcl-2 protein. The key sites of Bcl-2 protein were explored and a series of novel small molecule inhibitors were designed and synthesized. Active experiment. Results Eight new small molecule compounds were designed and synthesized. Their structures were confirmed by 1HNMR and 13CNMR. Conclusion All of the 8 compounds have obvious anti-tumor activity in vitro, and most of them are higher than the positive control paclitaxel.