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Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors.

Abstract：

:We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang L,Yang Y,Zhou H,Zheng Q,Li Y,Zheng S,Zhao S,Chen D,Fan C

doi

10.1016/j.ejmech.2015.08.026

subject

Has Abstract

pub_date

2015-09-18 00:00:00

pages

445-63

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(15)30210-5

journal_volume

102

pub_type

杂志文章

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