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有机化学
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有机化学 ›› 2015, Vol. 35 ›› Issue (11): 2377-2382.DOI: 10.6023/cjoc201506030 上一篇    下一篇

研究简报

伊马替尼衍生物的合成及细胞毒活性研究

陈仕杰a, 和龙a,b, 王雪微a, 龚显峰a, 张华a,b   

  1. a 黑龙江大学功能有机重点实验室 哈尔滨 150080;
    b 国药一心制药有限公司 长春 130012
  • 收稿日期:2015-06-25 修回日期:2015-07-27 发布日期:2015-08-26
  • 通讯作者: 张华 E-mail:zhanghua34@163.com
  • 基金资助:

    黑龙江省教育厅科学技术研究(No. 12521417)资助项目.

Synthesis and Cytotoxic Activity of Imatinib Derivatives

Chen Shijiea, He Longa,b, Wang Xueweia, Gong Xianfenga, Zhang Huaa,b   

  1. a Key Laboratory of Applied Organic, Heilongjiang University, Harbin 150080;
    b Sinopharm A-Think Pharmaceuticals Co., Ltd., Changchun 130012
  • Received:2015-06-25 Revised:2015-07-27 Published:2015-08-26
  • Supported by:

    Project supported by the Foundation of Heilongjiang Educational Committee (No. 12521417).

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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(HepG-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.

关键词: 伊马替尼衍生物, 合成, 四甲基偶氮唑盐(MTT)法

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, 13C 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 (HepG-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 (HepG-2) were comparable to those of imatinib.

Key words: imatinib derivatives, synthesis, methyl thiazolyl tetrazolium (MTT) assay