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ID: ALA4715818

Journal: Bioorg Med Chem

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

Authors: Hou W,Ren Y,Zhang Z,Sun H,Ma Y,Yan B

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 (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.

CiteXplore: 29523467

DOI: 10.1016/j.bmc.2018.02.022