Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor
Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor
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DOI：
10.1021/jm901877j
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发表时间：
2010-04-08
影响因子：
7.3
通讯作者：
Rauh, Daniel
中科院分区：
文献类型：
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作者：
Pawar, Vijaykumar G.;Sos, Martin L.;Rauh, Daniel
突变型受体酪氨酸激酶EGFR是一种经验证的和治疗上适合的基因型选择的肺癌患者的目标。在这里，我们提出了一系列的6-和7-取代的4-苯胺喹啉作为有效的I型抑制剂的临床相关的EGFR突变体的合成和生物学评价。喹啉类化合物3a和3e在生物化学试验中被发现是高活性的激酶抑制剂，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。
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.