Discovery of novel c-Met kinase inhibitors bearing a thieno[2,3-d]pyrimidine or furo[2,3-d]pyrimidine scaffold

被引：39

作者：

Zhao, Ailing ^{[2
]}

Gao, Xin ^{[1
]}

Wang, Yuanxiang ^{[2
]}

Ai, Jing ^{[1
]}

Wang, Ying ^{[1
]}

Chen, Yi ^{[1
]}

Geng, Meiyu ^{[1
]}

Zhang, Ao ^{[2
]}

机构：

[1] Chinese Acad Sci, SIMM, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China

[2] Chinese Acad Sci, SIMM, State Key Lab Drug Res, SOMCL, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2011年 / 19卷 / 13期

关键词：

RTK; c-Met; Thieno[2,3-d]pyrimidine; Furo[2,3-d]pyrimidine; Antitumor; FACTOR SCATTER FACTOR; TYROSINE KINASE; BIOLOGICAL EVALUATION; SELECTIVE INHIBITORS; GROWTH; POTENT; PHENOTYPE; CELLS; IDENTIFICATION; METASTASIS;

D O I：

10.1016/j.bmc.2011.05.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of thieno[2,3-d]pyrimidines and furo[2,3-d] pyrimidines were synthesized and evaluated for the c-Met inhibition. Thieno[2,3-d]pyrimidine 6b stood out as the most potent showing an IC(50) of 35.7 nM. This compound displayed high inhibitory effect on cell proliferation in BaF3-TPR-Met cells and showed high selectivity for c-Met family against other 14 tested kinases. However, compound 6b was found ineffective in the c-Met-dependent U-87MG human gliobastoma xenograft model that may be relevant to its poor PK profile. (C) 2011 Elsevier Ltd. All rights

引用

页码：3906 / 3918

页数：13

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