伊马替尼衍生物的合成及其抗肿瘤活性

以4-硝基-2-氨基甲苯为起始原料，经加成、缩合、环化和还原反应制得中间体N-(2-甲基-5-氨基苯基)-4-(3-吡啶基)嘧啶-2-胺(4)，再与取代酰氯反应，合成了7个新型伊马替尼衍生物（5a~5g），其结构经¹H NMR, ¹³C NMR和HR-MS 表征。采用四甲基偶氮唑盐(MTT)法考察了5对人肝癌细胞(HepG₂)、子宫颈癌细胞（Hela）、肺癌细胞（H460）和乳腺癌细胞（MCF-7）体外抑制活性。结果显示：5e体外抑制活性最优，其IC₅₀分别为10.90±1.00 μmol·L^-1； 8.51±0.90 μmol·L^-1； 13.15±1.11 μmol·L^-1； 14.75±0.78 μmol·L^-1。

Synthesis and Antitumor Activities of Imatinib Derivatives

Seven derivatives of imatinib (5a~5g) were prepared by condensation of substituted acid chlo-rides with N-(5-amino-2-methylphenyl )-4-(3-pyridyl )-2-pyrimidine amine, which was prepared from 2-methyl-5-nitroaniline through the reactions of addition , condensation , cyclization and reduction , respective-ly.The structures were characterized by 1 H NMR, 13 C NMR and HR-MS.The in vitro antitumor activities of 5a~5g against human hepatoma cells(HepG2), cervical cancer cells(Hela), lung cancer cells (H460) and breast cancer cells(MCF-7) were investgated by methyl thiazolyl tetrazolium (MTT) method.The re-sults demonstrated that 5e exhibited good inhibition activities with IC50of 10.90 ±1.00μmol· L-1, 8.51 ± 0.90μmol· L-1, 13.15 ±1.11μmol· L-1and 14.75 ±0.78μmol· L-1, respectively.