The discovery of N-(1,3-thiazol-2-yl)pyridin-2-amines as potent inhibitors of KDR kinase

Mark T Bilodeau; Leonard D Rodman; Georgia B McGaughey; Kathleen E Coll; Timothy J Koester; William F Hoffman; Randall W Hungate; Richard L Kendall; Rosemary C McFall; Keith W Rickert; Ruth Z Rutledge; Kenneth A Thomas

doi:10.1016/j.bmcl.2004.03.052

The discovery of N-(1,3-thiazol-2-yl)pyridin-2-amines as potent inhibitors of KDR kinase

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2941-5. doi: 10.1016/j.bmcl.2004.03.052.

Authors

Mark T Bilodeau¹, Leonard D Rodman, Georgia B McGaughey, Kathleen E Coll, Timothy J Koester, William F Hoffman, Randall W Hungate, Richard L Kendall, Rosemary C McFall, Keith W Rickert, Ruth Z Rutledge, Kenneth A Thomas

Affiliation

¹ Departments of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. mark_bilodeau@merck.com

PMID: 15125964
DOI: 10.1016/j.bmcl.2004.03.052

Abstract

An azo-dye lead was modified to a novel N-(1,3-thiazol-2-yl)pyridin-2-amine series of KDR kinase inhibitors through the use of rapid analog libraries. This new class has been found to be potent, selective, and of low molecular weight. Molecular modeling has postulated an interesting conformational preference and binding mode for these compounds in the active site of the enzyme.

MeSH terms

Amines / chemical synthesis
Amines / pharmacology*
Binding Sites
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Models, Molecular
Protein Binding
Protein Conformation / drug effects
Structure-Activity Relationship
Thermodynamics
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
Vascular Endothelial Growth Factor Receptor-2 / chemistry

Substances

Amines
Enzyme Inhibitors
Vascular Endothelial Growth Factor Receptor-2