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Synthesis and biological evaluation of novel tricyclic oxazine and oxazepine fused quinazolines. Part 2: Gefitinib analogs.

Abstract：

:Two series of novel tricyclic oxazine and oxazepine fused quinazolines have been designed and synthesized. The in vitro antitumor effect of the title compounds was screened on N87, A431, H1975, BT474 and Calu-3 cell lines. Compared to gefitinib and erlotinib, compounds 1a-1h were found to demonstrate more potent antitumor activities. Several derivatives could counteract EGF-induced phosphorylation of EGFR in cells, and their potency was comparable to the reference compounds. Compounds 1a-1f, 1h were chosen for further evaluation of EGFR and HER2 in vitro kinase inhibitory activity. Compounds 1c-1f, 1h effectively inhibited the in vitro kinase activity of EGFR and HER2 with similar efficacy as gefitinib and erlotinib.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Sun M,Zhao J,Chen X,Zong Z,Han J,Du Y,Sun H,Wang F

doi

10.1016/j.bmcl.2016.08.007

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

4842-4845

issue

19

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30817-4

journal_volume

26

pub_type

杂志文章

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