伊马替尼衍生物的合成及细胞毒活性研究

Synthesis and Cytotoxic Activity of Imatinib Derivatives

以3-乙酰基嘧啶、2-甲基-5-硝基苯胺为起始原料,经加成、缩合、环化、还原得到中间体N-(2-甲基-5-氨基苯基)-4-(3-吡啶基)嘧啶-2-胺(6),再与(L)-N-酰化-氨基酸缩合得到14个伊马替尼氨基酸衍生物7a^7n.目标化合物结构经过IR,1H NMR,13C NMR,HRMS等确证.采用四甲基偶氮唑盐(MTT)法考察了目标化合物对人白血病细胞(K562)、人肺癌细胞(A549)、人肝癌细胞(Hep G-2)体外抑制活性测试.结果显示化合物7a,7d,7e,7i,7j,7k,7l,7n体外抑制活性较高,与对照品伊马替尼相近.

Fourteen derivatives of imatinib have been prepared by condensation of（L）-N-acylation amino acid with N-（5-amino-2-methylphenyl）-4-（3-pyridyl）-2-pyrimidine amine（6）, which was prepared from 3-acetyl-pyrimidin and 2-methyl-5-nitroaniline through the reactions of addition, condensation, cyclization and reduction, respectively. The structures of all target compounds were characterized by IR, 1H NMR, 13 C NMR and HRMS techniques. They were evaluated for cytotoxic activity against human Leukemia cells（K562）, human non-small-cell-lung cancer cells lines（A549） and human hepatoma cell lines（Hep G-2） by methyl thiazolyl tetrazolium（MTT） method. The results showed the cytotoxic activities of compounds 7d, 7i, 7j, 7k, 7l, 7n against human Leukemia cells（K562） and human non-small-cell-lung cancer cell lines（A549）,compounds 7a, 7d, 7e against human hepatoma cell lines（Hep G-2） were comparable to those of imatinib.