5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase

被引：41

作者：

Ballard, P

Bradbury, RH

Hennequin, LFA

Hickinson, DM

Johnson, PD

Kettle, JG

Klinowska, T

Morgentin, R

Ogilvie, DJ

Olivier, A

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 19期

关键词：

anilinoquinazoline; erbB2; receptor tyrosine kinase;

D O I：

10.1016/j.bmcl.2005.06.068

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from a 6,7-substituted quinazoline lead 4, optimisation of 5-substituted quinazolines containing an extended aniline motif led to potent and selective inhibitors of erbB2 receptor tyrosine kinase, and a representative compound 12a inhibited tumour growth in a mouse xenograft model. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4226 / 4229

页数：4

共 21 条

[1]

Baselga J, 1998, CANCER RES, V58, P2825

[2]

Bradbury R.H., 2005, [No title captured], Patent No. [2005012290A1, 2005012290]

[3]

BROWN DS, 1996, Patent No. 9615118

[4] Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease [J].

Cobleigh, MA ;

Vogel, CL ;

Tripathy, D ;

Robert, NJ ;

Scholl, S ;

Fehrenbacher, L ;

Wolter, JM ;

Paton, V ;

Shak, S ;

Lieberman, G ;

Slamon, DJ .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (09) :2639-2648

[5]

Cockerill G. S., 1998, PCT Int. Appl., Patent No. [WO 9802434 Al, 9802434]

[6] Targeting the HER-kinase axis in cancer [J].

Gross, ME ;

Shazer, RL ;

Agus, DB .

SEMINARS IN ONCOLOGY, 2004, 31 (01) :9-20

[7]

Hennequin L.A., 2003, [No title captured], Patent No. [2003040109A2, 2003040109, WO 2003040109 A2]

[8] Timeline - Gefitinib - a novel targeted approach to treating cancer [J].

Herbst, RS ;

Fukuoka, M ;

Baselga, J .

NATURE REVIEWS CANCER, 2004, 4 (12) :956-965

[9]

KATH JC, 2003, 226 NAT M AM CHEM SO

[10]

NEWKOME GR, 1984, SYNTHESIS-STUTTGART, P676

← 1 2 3 →