Synthesis and SAR of potent EGFR/erbB2 dual inhibitors

Yue-Mei Zhang; Stuart Cockerill; Stephen B Guntrip; David Rusnak; Kathryn Smith; Dana Vanderwall; Edgar Wood; Karen Lackey

doi:10.1016/j.bmcl.2003.10.010

Synthesis and SAR of potent EGFR/erbB2 dual inhibitors

Bioorg Med Chem Lett. 2004 Jan 5;14(1):111-4. doi: 10.1016/j.bmcl.2003.10.010.

Authors

Yue-Mei Zhang¹, Stuart Cockerill, Stephen B Guntrip, David Rusnak, Kathryn Smith, Dana Vanderwall, Edgar Wood, Karen Lackey

Affiliation

¹ GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA.

PMID: 14684309
DOI: 10.1016/j.bmcl.2003.10.010

Abstract

A series of 6-alkoxy-4-anilinoquinazoline compounds was prepared and evaluated for in vitro inhibition of the erbB2 and EGFR kinase activity. The IC(50) values of the best compounds were below 0.10 uM. Further, several of these compounds inhibit the growth of erbB2 and EGFR over-expressing tumor cell lines at concentrations below 1 uM.

MeSH terms

Binding Sites / drug effects
Binding Sites / physiology
Cell Line, Tumor
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
ErbB Receptors
Glycoproteins / antagonists & inhibitors*
Glycoproteins / metabolism
Humans
Receptor, ErbB-2 / antagonists & inhibitors*
Receptor, ErbB-2 / metabolism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Glycoproteins
EGFR protein, human
ErbB Receptors
Receptor, ErbB-2