【摘要】 以临床化合物NX-5948为先导结构，通过引入并环代替酰胺的骨架跃迁策略对其进行结构改造，设计并合成了一系列新型BTK PROTACs(化合物I～IV)，其结构经MS谱和~1H-NMR确认，通过细胞增殖检测试剂盒(MTS)法和蛋白质免疫印迹法(Western Blot,WB)分别测定目标化合物的细胞增殖抑制活性和BTK蛋白降解能力。结果显示，所有目标化合物对淋巴瘤Mino细胞内BTK的降解能力不低于NX-5948，对淋巴瘤OCI-LY10细胞的增殖抑制活性明显强于NX-5948。更多还原

【Abstract】 Taking the clinical compound NX-5948 as the lead compound,we analyzed its structure,and successfully synthesized a series of new BTK PROTACs( compounds I to IV) by introducing the skeleton transition idea of ring instead of amide. Their structures were confirmed by MS spectra and ~1H-NMR. The cell proliferation inhibition activity and BTK degradation activity of the target compounds were determined by the cell proliferation assay kit( MTS) and western blot( WB),respectively.The results showed that the degradation ability of all target compounds for BTK in Mino cells was not weaker than that of NX-5948,and the proliferation inhibition activity of all target compounds against OCI-LY10 cells was significantly stronger than that of NX-5948.更多还原