伊马替尼衍生物的合成及细胞毒活性研究

Syntheses and Cytotoxic Activities 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、还原得到中间体伊马替胺(6),再与异氰酸酯和芳酰基异硫氰酸酯胺解得到脲类(7a^7e)和芳酰基硫脲类(8a^8g)共12个化合物。目标化合物经过IR、1H NMR、13C NMR、HRMS等结构确证。采用四甲基偶氮唑盐(MTT)法考察目标化合物细胞毒活性,结果显示,目标化合物对所选肿瘤细胞的增殖活性具有一定抑制作用,其中化合物7d、7e、8d对人白血病细胞(K562)和人肝癌细胞(Hep G2)的抑制活性接近伊马替尼。

A series of novel imatinib derivatives urea （7a -7e） and aroyl thiourea （8a -8g） were synthesized using 3-acetylpyrimidine, and 2-methyl-5-nitroaniline as starting material via addition, condensation, cyclization, reduction, then reaction with isocyanates and isothiocyanates. The structures of all target compounds were confirmed by IR, ZH NMR, 13C NMR and HRMS. Their cytotoxic activities against human Leukemia ceils（K562） lines and human hepatoma cell lines （HepG2） were evaluated by methyl thiazolyl tetrazolium （MTT） method, It shows that they have certain inhibitory activity, especially compounds 7d, 7c, 8d have approximation inhibitory activities on K562 and HepG2 with imatinib.