Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series

被引：180

作者：

Petrov, Kimberly G. ^{[1
]}

Zhang, Yue-Mei ^{[1
]}

Carter, Malcolm ^{[1
]}

Cockerill, G. Stuart ^{[1
]}

Dickerson, Scott ^{[1
]}

Gauthier, Cassandra A. ^{[1
]}

Guo, Yu ^{[1
]}

Mook, Robert A., Jr. ^{[1
]}

Rusnak, David W. ^{[1
]}

Walker, Ann L. ^{[1
]}

Wood, Edgar R. ^{[1
]}

Lackey, Karen E. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Res Triangle Pk, NC USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 17期

关键词：

ErbB-1 tyrosine kinase inhibitors; ErbB-2 tyrosine kinase inhibitors; EGFR kinase inhibitors; quinazoline; lapatinib;

D O I：

10.1016/j.bmcl.2006.05.090

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：4686 / 4691

页数：6

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