新型喹唑啉衍生物，带有各种 6-苯甲酰胺取代基，作为高度选择性和有效的 EGFR 抑制剂。
Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors.
机构信息
College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences (NIBS), Beijing 102206, China.
National Institute of Biological Sciences (NIBS), Beijing 102206, China.
出版信息
Bioorg Med Chem. 2018 May 1;26(8):1740-1750. doi: 10.1016/j.bmc.2018.02.022. Epub 2018 Feb 16.
A series of novel quinazoline derivatives bearing various C-6 benzamide substituents were synthesized and evaluated as EGFR inhibitors, and most showed significant inhibitory potency against EGFR kinase. In particular, compound 6g possessed potent inhibitory activity against EGFR wild-type (IC = 5 nM), and strong antiproliferative activity against HCC827 and Ba/F3 (L858R) cell lines. Kinase profiling against a panel of 365 kinases showed that 6g was highly selective for EGFR. Furthermore, 6g showed desirable properties in assays of liver microsome metabolic stability and cytochromes P450 inhibition and preliminary pharmacokinetic study. The overall attractive profile of 6g made it an interesting compound for further development.
一系列新型含各种 C-6 苯甲酰胺取代基的喹唑啉衍生物被合成并评估为 EGFR 抑制剂，大多数对 EGFR 激酶表现出显著的抑制活性。特别是化合物 6g 对 EGFR 野生型（IC=5nM）具有很强的抑制活性，对 HCC827 和 Ba/F3（L858R）细胞系也具有很强的抗增殖活性。对 365 种激酶的激酶谱分析表明，6g 对 EGFR 具有高度选择性。此外，6g 在肝微粒体代谢稳定性和细胞色素 P450 抑制试验以及初步药代动力学研究中表现出良好的性质。6g 的整体有吸引力的特征使其成为进一步开发的一个有趣的化合物。
Zotero 插件