含Schiff碱结构的2-芳胺基嘧啶衍生物的合成及体外抗肿瘤活性研究

Synthesis and Biological Evaluation of 2-Phenylaminopyrimidine Schiff Base Derivatives

以邻甲基苯胺、3-乙酰基吡啶、N,N二甲基甲酰胺二甲基缩醛为起始原料,经硝化、加成、环合、还原、缩合等6步反应合成目标化合物。以伊马替尼为阳性对照药,采用台盼蓝排染法,以慢性粒细胞白血病K562细胞为测试细胞株,对目标化合物进行体外抗白血病活性评价。所合成的18个化合物结构经1HNMR和MS确证。初步药理实验结果表明,目标化合物对K562细胞有一定的抗肿瘤活性,但低于阳性对照药伊马替尼和先导化合物。酰胺键结构对保持活性有重要的影响,是药物与受体的重要结合位点。

The target compounds were synthesized by 6 steps with o-toluidine,3-acetylpyridine,DMF-DMA as the start materials.These compounds were tested to inhibit human leukemia cell lines K562 using trypan blue exclusion staining with Imatinib as positive control.The structures of the novel compounds were confirmed by -1 HNMR and MS.Preliminary pharmacological results showed that all of the compounds possessed potent antitumor activities but lower than Imatinib and lead compound.We considered that amide link age is must be required to maintain the activity.