目的 設(shè)計(jì)并合成達(dá)沙替尼衍生物，并研究其抗腫瘤活性。方法 以達(dá)沙替尼、四乙二醇和五乙二醇單甲醚為原料，通過取代反應(yīng)合成達(dá)沙替尼衍生物，并考察目標(biāo)化合物對K562細(xì)胞增殖的抑制作用。結(jié)果 設(shè)計(jì)并合成了4個達(dá)沙替尼衍生物，結(jié)構(gòu)經(jīng)¹H-NMR和MALDI-TOF-MS確證。其中2個化合物JK220324和JK220326的抗腫瘤活性較達(dá)沙替尼高，IC₅₀分別為0.50、0.34 nmol/L，較達(dá)沙替尼（0.76 nmol/L）低。結(jié)論 達(dá)沙替尼用小分子聚乙二醇衍生，有望獲得活性更好、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.

天津市科技計(jì)劃項(xiàng)目（15PTSYJC00220）