School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210009, Jiangsu, China.
Chem Biol Drug Des. 2011 Dec;78(6):932-40. doi: 10.1111/j.1747-0285.2011.01234.x. Epub 2011 Oct 24.
Here, we describe the design and synthesis of two series of 4-pyrrylamino quinazolines as new analogs of the epidermal growth factor receptor inhibitor gefitinib. In vitro antitumor activity of these novel compounds against pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated. Compared with the parental gefitinib, all 18 derivatives show a greatly increased cytotoxicity to cancer cells. In vitro kinase inhibitory activity on epidermal growth factor receptor was also investigated. Among them, compounds GI-6, GII-4, GII-6, GII-8, and GII-9 are more potential receptor tyrosine kinase (RTK) inhibitors. Based on these results, we propose simple structure-activity relationship to provide information for designing and developing more potent antitumor agents.
在这里，我们描述了两个系列的 4-嘧啶基喹唑啉的设计和合成，它们是表皮生长因子受体抑制剂吉非替尼的新型类似物。评估了这些新型化合物对胰腺（Miapaca2）和前列腺（DU145）癌细胞系的体外抗肿瘤活性。与亲本吉非替尼相比，所有 18 个衍生物对癌细胞的细胞毒性大大增加。还研究了它们对表皮生长因子受体的体外激酶抑制活性。其中，化合物 GI-6、GII-4、GII-6、GII-8 和 GII-9 是更有潜力的受体酪氨酸激酶（RTK）抑制剂。基于这些结果，我们提出了简单的构效关系，为设计和开发更有效的抗肿瘤药物提供信息。
