Inhibitors of epidermal growth factor receptor tyrosine kinase: Optimisation of potency and in vivo pharmacokinetics

被引：37

作者：

Ballard, Peter

Bradbury, Robert H.

Harris, Craig S.

Hennequin, Laurent F. A.

Hickinson, Mark

Kettle, Jason G.

Kendrew, Jane

Klinowska, Teresa

Ogilvie, Donald J.

Pearson, Stuart E.

Williams, Emma J.

Wilson, Ingrid

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 18期

关键词：

EGF; kinase; inhibitor; DMPK;

D O I：

10.1016/j.bmcl.2006.06.054

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

The structure-activity and structure-property relationships of anilinoquinazoline inhibitors of EGFR were investigated. Strategies to lower volume of distribution and shorten half-life through structure and pK(a) modulation are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：4908 / 4912

页数：5

相关论文

共 15 条

[1]

Studies leading to the identification of ZD1839 (Iressa™):: An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer [J].

Barker, AJ ;

Gibson, KH ;

Grundy, W ;

Godfrey, AA ;

Barlow, JJ ;

Healy, MP ;

Woodburn, JR ;

Ashton, SE ;

Curry, BJ ;

Scarlett, L ;

Henthorn, L ;

Richards, L .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (14) :1911-1914

[2]

Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types [J].

Baselga, J ;

Rischin, D ;

Ranson, M ;

Calvert, H ;

Raymond, E ;

Kieback, DG ;

Kaye, SB ;

Gianni, L ;

Harris, A ;

Bjork, T ;

Averbuch, SD ;

Feyereislova, A ;

Swaisland, H ;

Rojo, F ;

Albanell, J .

JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (21) :4292-4302

[3]

United States Food and Drug Administration drug approval summary: Gefitinib (ZD1839; Iressa) tablets [J].

Cohen, MH ;

Williams, GA ;

Sridhara, R ;

Chen, G ;

McGuinn, WD ;

Morse, D ;

Abraham, S ;

Rahman, A ;

Liang, CY ;

Lostritto, R ;

Baird, A ;

Pazdur, R .

CLINICAL CANCER RESEARCH, 2004, 10 (04) :1212-1218

[4]

Novel 4-anilinoquinazolines with C-7 basic side chains:: Design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors [J].

Hennequin, LF ;

Stokes, ESE ;

Thomas, AP ;

Johnstone, C ;

Plé, PA ;

Ogilvie, DJ ;

Dukes, M ;

Wedge, SR ;

Kendrew, J ;

Curwen, JO .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (06) :1300-1312

[5]

HENNEQUIN LFA, Patent No. 2003040109

[6]

ZD6474 - clinical experience to date [J].

Heymach, JV .

BRITISH JOURNAL OF CANCER, 2005, 92 (Suppl 1) :S14-S20

[7]

ERBB receptors and cancer: The complexity of targeted inhibitors [J].

Hynes, NE ;

Lane, HA .

NATURE REVIEWS CANCER, 2005, 5 (05) :341-354

[8]

Pharmacokinetics of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat and dog [J].

McKillop, D ;

Partridge, EA ;

Hutchison, M ;

Rhead, SA ;

Parry, AC ;

Bardsley, J ;

Woodman, HM ;

Swaisland, HC .

XENOBIOTICA, 2004, 34 (10) :901-915

[9]

A Multicenter phase II trial of ZD6474, a vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinase inhibitor, in patients with previously treated metastatic breast cancer [J].

Miller, KD ;

Trigo, JM ;

Wheeler, C ;

Barge, A ;

Rowbottom, J ;

Sledge, G ;

Baselga, J .

CLINICAL CANCER RESEARCH, 2005, 11 (09) :3369-3376

[10]

MORTLOCK AA, Patent No. 2001021596