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Novel hydrazone moiety-bearing aminopyrimidines as selective inhibitors of epidermal growth factor receptor T790M mutant.

Abstract：

:The epidermal growth factor receptor (EGFR) T790M mutant is found in approximately 50% of clinically acquired resistance to gefitinib among patients with non-small cell lung cancer (NSCLC). Here, a series of novel aminopyrimidines bearing a hydrazone moiety were identified as potent and selective EGFR inhibitors. Compounds 14a, 15g, and 15i potently inhibited all EGFR mutants including EGFR T790M/L858R, EGFR T790M/delE746_A750, and EGFR T790M while they showed weak effects on the wild type (WT) EGFR. In addition, these compounds effectively suppressed proliferation of gefitinib-resistant H1975 (EGFR T790M/L858R) cells but were less potent against A549 (WT EGFR and k-Ras mutation) and HT-29 (non-special gene type) cells, showing a high safety index. Therefore, 14a, 15g, and 15i might be promising candidates to overcome drug resistance mediated by the EGFR T790M mutant.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Qin M,Wang T,Xu B,Ma Z,Jiang N,Xie H,Gong P,Zhao Y

doi

10.1016/j.ejmech.2015.09.031

subject

Has Abstract

pub_date

2015-11-02 00:00:00

pages

115-26

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)30275-0

journal_volume

104

pub_type

杂志文章

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