A new series of neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase

被引：21

作者：

Barlaam, Bernard ^{[1
]}

Ballard, Peter ^{[2
]}

Bradbury, Robert H. ^{[2
]}

Ducray, Richard ^{[1
]}

Germain, Herve ^{[1
]}

Hickinson, D. Mark ^{[2
]}

Hudson, Kevin ^{[2
]}

Kettle, Jason G. ^{[2
]}

Klinowska, Teresa ^{[2
]}

Magnien, Francoise ^{[1
]}

Ogilvie, Donald J. ^{[2
]}

Olivier, Annie ^{[1
]}

Pearson, Stuart E. ^{[2
]}

Scott, James S. ^{[2
]}

Suleman, Abid ^{[2
]}

Trigwell, Cath B. ^{[2
]}

Vautier, Michel ^{[1
]}

Whittaker, Robin D. ^{[2
]}

Wood, Robin ^{[2
]}

机构：

[1] AstraZeneca, Ctr Rech, F-51689 Reims 2, France

[2] AstraZeneca, Canc & Infect Res, Macclesfield SK10 4TG, Cheshire, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 02期

关键词：

anilinoquinazoline; C-5; substitution; erbB2 kinase inhibitor;

D O I：

10.1016/j.bmcl.2007.11.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from initial lead 1 containing a basic 5-substituent, optimisation of the glycolamide-derived neutral 5-substituent led to potent inhibitors of erbB2 with good pharmacokinetics. Representative compounds 19 and 21 inhibited phosphorylation of erbB2 in a mouse BT474C xenograft model after oral administration. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：674 / 678

页数：5

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