联杂环类新型蛋白激酶抑制剂的设计、合成及抗癌活性的研究

Design,syntheses and anticancer activity evaluation of novel hetero-Biatyl protein kinase inhibitors

目的:分析现有的蛋白激酶抑制剂的结构特征,将联杂环(嘧啶联苯)确立为母核骨架的模型,围绕嘧啶联苯这个骨架,在该模型基础上设计并合成新型的类药性小分子。方法:采用拼合原理反复优化嘧啶联苯这个母环模型,得到一系列结构新颖的联杂环类化合物。采用噻唑蓝法对所合成的化合物进行体外抗肿瘤活性的初步测定。结果:试验结果显示该类联杂环化合物对肿瘤细胞的增长具有抑制作用。结论:通过采用确定中心药效团并对其衍生化的方法,发现了一系列以嘧啶联苯为中心药效团的新型抗肿瘤化合物。

Objective.. To establishing pharmacophore models by analyzing known inhibitors and allosteric conforma tion, design and synthesize a series of drug-like small molecule library. Methods：We synthesized some novel protein kinase inhibitors of the phenylpyrimidine core. Tested their inhibitory activity against HeLa cells in cell assays. Results： Preliminary re suits indicated that some of these phenylpyrimidine derivatives possess potent anti-proliferative activities,with IC50 data in the micromolar range. Conclusion：The drug like molecule library approach is an effective method for the identification of novel hetero-biatyl anti-tumor compounds.