伊马替尼衍生物的合成及其抗肿瘤活性

摘要

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.%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1 H NMR,13 C 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(HepG-2)、子宫颈癌细胞(He-la)、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±1.00μmol·L-1;8.51±0.90μmol·L-1;13.15±1.11μmol·L-1;14.75±0.78μmol·L-1.