高等学校化学学报Issue(9)：1694-1701,8.DOI:10.7503/cjcu20150404
嘧啶联苯类化合物的设计、合成及抗肿瘤活性
Design and Synthesis of Phenylpyrimidine and Their Anticancer Activity
摘要
Abstract
Allosteric kinase inhibitors modulate kinase activities by inducing and stabilizing the inactive con-formations of the targets. In comparison to ATP competitive inhibitors, this type inhibitors exhibit better selec-tivity and higher efficacy, and have shown to be safe and effective treatments for various forms of cancers in the clinics. Based on the X-ray co-crystal structures of reported allosteric kinase inhibitors bound to thecorre-sponding protein kinases, a bi-cyclic pharmacophore model was proposed. 19 new phenylpyrimidine deriva-tives were designed and synthesized from 2,4-diamino-5-methylpyrimidine. The inhibitory effects of these com-pounds against human breast cancer cell(MCF-7) proliferation were evaluated using MTT method. The leader compounds, 8c and 9c, were identified showing IC50 of 0. 224 and 0. 113 μmol/L, respectively.关键词
嘧啶联苯/蛋白激酶/变构抑制剂/抗肿瘤活性Key words
Phenylpyrimidine/Protein kinase/Allosteric kinase inhibitor/Antitumor activity分类
化学化工引用本文复制引用
周皓,段志刚,赵爽,宝梅英,李志伟,裴亚中..嘧啶联苯类化合物的设计、合成及抗肿瘤活性[J].高等学校化学学报,2015,(9):1694-1701,8.基金项目
国家自然科学基金(批准号:81172914,81071743)、吉林大学唐敖庆教授启动资金和吉林省人才开发基金资助 （批准号:81172914,81071743）
