目的 设计并合成达沙替尼衍生物，并研究其抗肿瘤活性。方法 以达沙替尼、四乙二醇和五乙二醇单甲醚为原料，通过取代反应合成达沙替尼衍生物，并考察目标化合物对K562细胞增殖的抑制作用。结果 设计并合成了4个达沙替尼衍生物，结构经¹H-NMR和MALDI-TOF-MS确证。其中2个化合物JK220324和JK220326的抗肿瘤活性较达沙替尼高，IC₅₀分别为0.50、0.34 nmol/L，较达沙替尼（0.76 nmol/L）低。结论 达沙替尼用小分子聚乙二醇衍生，有望获得活性更好、毒性更小的化合物。

Objective To design and synthesize dasatinib derivatives, and study their anti-tumor activities. Methods Dasatinib, tetraethylene glycol, pentaethylene glycol monomethyl ether, and were used as materials to synthesize dasatinib derivatives by substitution reaction, and the anti-tumor activities against K562 cells were tested. Results Four dasatinib derivatives were designed and synthesized, and their structures were confirmed by ¹H-NMR and MALDI-TOF-MS. In which the anti-tumor activities of two target compounds JK220324 and JK220326 were higher than dasatinib, and their IC₅₀ were 0.50 and 0.34 nmol/L, which were lower than that of dasatinib (0.76 nmol/L). Conclusion Dasatinib derived by low molecular polyethylene glycol derivatives is expected to acquire the compound with better activities and less toxicity.

天津市科技计划项目（15PTSYJC00220）