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

Peter Ballard; Robert H Bradbury; Laurent F A Hennequin; D Mark Hickinson; Paul D Johnson; Jason G Kettle; Teresa Klinowska; Remy Morgentin; Donald J Ogilvie; Annie Olivier

doi:10.1016/j.bmcl.2005.06.068

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

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4226-9. doi: 10.1016/j.bmcl.2005.06.068.

Authors

Peter Ballard¹, Robert H Bradbury, Laurent F A Hennequin, D Mark Hickinson, Paul D Johnson, Jason G Kettle, Teresa Klinowska, Remy Morgentin, Donald J Ogilvie, Annie Olivier

Affiliation

¹ Cancer and Infection Research, AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.

PMID: 16055332
DOI: 10.1016/j.bmcl.2005.06.068

Abstract

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.

MeSH terms

Administration, Oral
Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / pharmacology
Carrier Proteins / antagonists & inhibitors*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology
Inhibitory Concentration 50
Intracellular Signaling Peptides and Proteins
Mice
Neoplasms, Experimental / drug therapy
Quinazolines / chemical synthesis*
Quinazolines / pharmacokinetics
Quinazolines / pharmacology
Structure-Activity Relationship
Transplantation, Heterologous
Tumor Burden / drug effects

Substances

Antineoplastic Agents
Carrier Proteins
Enzyme Inhibitors
Erbb2ip protein, mouse
Intracellular Signaling Peptides and Proteins
Quinazolines