State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5870-5. doi: 10.1016/j.bmcl.2012.07.079. Epub 2012 Jul 31.
It had been reported that some dioxygenated rings fusing with the quinazoline scaffold could lead to new EGFR inhibitors. Based on this, several kinds of oxygenated alkane quinazoline derivatives were synthetized and evaluated as EGFR inhibitors. Their antiproliferative activities were tested against four cancer cell lines: A431, MCF-7, A549, and B16-F10. Most derivatives could counteract EGF-induced EGFR phosphorylation, and their potency was comparable to the reference compound Erlotinib. The size of the fused dioxygenated ring was crucial for the biological activity and the heptatomic ring derivative 19 showed potent in vitro inhibitory activity in the enzymatic assay as well as in the cellular assay.
据报道，某些与喹唑啉骨架稠合的双加氧环可导致新型 EGFR 抑制剂的产生。基于这一理论，我们合成了几种含氧烷烃喹唑啉衍生物，并将其作为 EGFR 抑制剂进行了评估。对它们针对四种癌细胞系（A431、MCF-7、A549 和 B16-F10）的抗增殖活性进行了测试。大多数衍生物可拮抗 EGF 诱导的 EGFR 磷酸化，其活性与参比化合物厄洛替尼相当。稠合双加氧环的大小对于生物活性至关重要，七元环衍生物 19 在酶促测定和细胞测定中均表现出很强的体外抑制活性。
