Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for VEGFR-2 and PDGFR tyrosine kinases

Patrick A Plé; Frédéric Jung; Sue Ashton; Laurent Hennequin; Romuald Laine; Rémy Morgentin; Georges Pasquet; Sian Taylor

doi:10.1016/j.bmcl.2011.11.019

Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for VEGFR-2 and PDGFR tyrosine kinases

Bioorg Med Chem Lett. 2012 Jan 1;22(1):262-6. doi: 10.1016/j.bmcl.2011.11.019. Epub 2011 Nov 12.

Authors

Patrick A Plé¹, Frédéric Jung, Sue Ashton, Laurent Hennequin, Romuald Laine, Rémy Morgentin, Georges Pasquet, Sian Taylor

Affiliation

¹ AstraZeneca, Centre de Recherches, B.P. 1050, 51689 Reims Cedex 2, France. [email protected]

PMID: 22153662
DOI: 10.1016/j.bmcl.2011.11.019

Abstract

A new series of Quinazoline Ether Inhibitor which potently inhibits VEGFR-2 and PDGFR tyrosine kinases is described here. In vitro, pharmacokinetics and in vivo evaluations led to the selection of AZD2932.

MeSH terms

Algorithms
Animals
Chemistry, Pharmaceutical / methods
Dogs
Drug Design
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Ethers / chemical synthesis*
Ethers / pharmacology*
Female
Humans
Inhibitory Concentration 50
Male
Models, Chemical
Phosphorylation
Quinazolines / chemical synthesis*
Quinazolines / pharmacology
Rats
Receptor, Platelet-Derived Growth Factor beta / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

AZD2932
Enzyme Inhibitors
Ethers
Quinazolines
Receptor, Platelet-Derived Growth Factor beta
Vascular Endothelial Growth Factor Receptor-2