【摘要】 通过研究BGB-11417与靶蛋白结合的相互作用，创造性的在P2口袋引入并环，合成了6个结构新颖的BCL-2抑制剂，产物经1 H NMR和MS确证。以时间分辨荧光共振能量转移法(TR-FRET)测定目标化合物对BCL-2蛋白及BCL-2突变蛋白G101V和D103Y的体外抑制活性。活性结果表明化合物A、化合物B和化合物D对BCL-2及其突变蛋白G101V和D103Y有较好的抑制活性，可为合成活性更高的BCL-2抑制剂提供参考。更多还原

【Abstract】 To synthesize a series of novel BCL-2 inhibitors and to determine their anticancer activity.By studying the interaction between BGB-11417 and BCL-2 protein, we creatively introduce bicyclic structure into P2 pocket.Six novel BCL-2 inhibitors were synthesized and their structures were confirmed by ~1H NMR spectra and MS.The inhibitory activity of the target compounds on BCL-2 and its mutant proteins G101V and D103Y in vitro was determined by time-resolved fluorescence resonance energy transfer method(TR-FRET).The results of biological evaluation indicated that compound A,compound B and compound D showed potent anticancer activities, which could provide a reference for synthesizing BCL-2 inhibitors with higher activity.更多还原