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目的 为进一步研究CNX-774及引入新共价交联基团的类似物在布鲁顿氏酪氨酸蛋白激酶(Bruton's tyrosine kinase,BTK)相关细胞上的生物活性,设计合成并筛选具有较好活性的化合物.方法 通过酰胺缩合、羟醛缩合等策略得到CNX-774的类似物,在几种淋巴瘤和HeLa细胞系上进行活性评价.结果通过简单的修饰得到了新的CNX-774的类似物1 ～17,其结构经氢谱、碳谱和质谱确认.在IgE多发性骨髓瘤(IgE MM)上化合物1和3的抑制率大于CNX-774;在Ramos、HBL-1和HeLa细胞上化合物1和3对Ramos的抑制活性较好;在HeLa细胞上化合物1和3展现出与CNX-774类似或较低的生物活性.结论化合物1和 3在IgE MM、Ramos上都表现出不错的分子活性,在HeLa细胞上也表现出低毒的结果,表明化合物1和3可以作为潜在的治疗BTK相关淋巴瘤的抑制剂.分子对接的结果也一定程度上解释了类似物与BTK的相互作用.“,”Bruton's tyrosine kinase(BTK) plays an important role in the lymphoma cell lines. In order to improve the activities and explore the effects of warheads in different BTK-related cell lines,a series of analogues were obtained via simple modifications of CNX-774, a BTK inhibitor. All analogues were evaluated on IgE multiple myeloma cell line at 200 nmol-L-1. Compounds 1 and 3 showed better inhibition than CNX-774,and were further tested on Ramos,HBL-1 and HeLa cell lines. It was showed that compounds 1 and 3 were the most potential molecules. Compared to CNX-774,they showed more excellent inhibition to IgE MM and Ramos cell lines, and possessed similar or even lower cytotoxicity in HeLa cell line. Compounds 1 and 3 would be valuable covalent molecules for treatment of BTK-related lymphomas. The docking results could explain their good activity.