2. Academic Validation
  3. Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors

Novel quinazoline derivatives bearing various 6-benzamide moieties as highly selective and potent EGFR inhibitors

  • Bioorg Med Chem. 2018 May 1;26(8):1740-1750. doi: 10.1016/j.bmc.2018.02.022.
Weijie Hou 1,  Yan Ren 2,  Zhenhua Zhang 3,  Huan Sun 2,  Yongfen Ma 2,  Bo Yan 2
Affiliations

Affiliations

  • 1 College of Life Sciences, Beijing Normal University, Beijing 100875, China; National Institute of Biological Sciences (NIBS), Beijing 102206, China. Electronic address: houweijie@nibs.ac.cn.
  • 2 National Institute of Biological Sciences (NIBS), Beijing 102206, China.
  • 3 Beijing Advanced Innovation Center for Food Nutrition and Human Health, Department of Applied Chemistry, China Agricultural University, Beijing 100193, China.
PMID: 29523467 DOI: 10.1016/j.bmc.2018.02.022
Abstract

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 (IC50 = 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.

Keywords

Anti-cancer; EGFR; High selectivity; Kinase inhibitor; Quinazoline.

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