title: The discovery of N-(1,3-thiazol-2-yl)pyridin-2-amines as potent inhibitors of KDR kinase.
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.
authors.affiliation: Departments of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. mark_bilodeau@merck.com
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Rodman
authors.forename: Georgia B
authors.initials: GB
authors.lastname: McGaughey
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Coll
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koester
authors.forename: William F
authors.initials: WF
authors.lastname: Hoffman
authors.forename: Randall W
authors.initials: RW
authors.lastname: Hungate
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kendall
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: McFall
authors.forename: Keith W
authors.initials: KW
authors.lastname: Rickert
authors.forename: Ruth Z
authors.initials: RZ
authors.lastname: Rutledge
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Thomas
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2