当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis and pharmacological evaluation of N4,N6-disubstituted pyrimidine-4,6-diamine derivatives as potent EGFR inhibitors in non-small cell lung cancer.

Design, synthesis and pharmacological evaluation of N4,N6-disubstituted pyrimidine-4,6-diamine derivatives as potent EGFR inhibitors in non-small cell lung cancer.

Abstract：

:A novel series of 4, 6-disubstituted pyrimidines derivatives were designed, synthesized, and evaluated as epidermal growth factor receptor (EGFR) inhibitors for non-small cell lung cancer(NSCLC). 4, 6-disubstituted pyrimidines as core structure was utilized to substitute the lead structure AZD3759 of the quinazoline basic skeleton via an approach involving scaffold hopping. It was found that compound Yfq07 exhibited the best inhibitory effect compared with AZD3759 in vitro and in vivo: Yfq07 exhibited a competitive ATP inhibitory effect, multiple target effects, and further featured a stronger activity against H3255, A431, HCC827, PC-9 and H1975 compared to AZD3759. Moreover, a stronger pro-apoptotic effect, inhibition of cell G2/M phase on A431, H3255, HCC827 and H1975 could also be observed. In this study, the ultimate goal was changing the core structure to improve other epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) properties while retaining the overall potency. Yfq07 was further explored as an effective 4, 6-pyrimidine anticancer agent for the treatment of human NSCLC.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Zhang Y,Lv H,Luo L,Xu Y,Pan Y,Wang Y,Lin H,Xiong J,Guo P,Zhang J,Li X,Ye F

doi

10.1016/j.ejmech.2018.08.031

subject

Has Abstract

pub_date

2018-09-05 00:00:00

pages

1300-1325

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(18)30699-8

journal_volume

157

pub_type

杂志文章

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