Chemical Genomics Centre of the Max Planck Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany.
J Med Chem. 2010 Apr 8;53(7):2892-901. doi: 10.1021/jm901877j.
The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.
突变型受体酪氨酸激酶 EGFR 是一个经过验证的治疗靶点，适用于基因选择的肺癌患者。在这里，我们展示了一系列 6-和 7-取代的 4-苯胺喹啉的合成和生物学评价，作为临床相关的 EGFR 突变型的有效 I 型抑制剂。喹啉 3a 和 3e 在生化测定中被发现是高度有效的激酶抑制剂，并进一步研究了它们对 EGFR 依赖性 Ba/F3 细胞和非小细胞肺癌 (NSCLC) 细胞系的生物学效应。
