title: Potent 2-[(pyrimidin-4-yl)amine}-1,3-thiazole-5-carbonitrile-based inhibitors of VEGFR-2 (KDR) kinase.
abstract: Pyrimidino-thiazolyl carbonitriles were prepared that are potent VEGFR-2 (KDR) kinase inhibitors. The modification of lead structures resulted in 3m which exhibited the best overall profile in KDR inhibitory activity, iv/po pharmacokinetics, and reduced hERG affinity.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. jack_sisko@merck.com
authors.forename: John T
authors.initials: JT
authors.lastname: Sisko
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Tucker
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Buser
authors.forename: Patrice A
authors.initials: PA
authors.lastname: Ciecko
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Coll
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandes
authors.forename: Jackson B
authors.initials: JB
authors.lastname: Gibbs
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koester
authors.forename: Nancy
authors.initials: N
authors.lastname: Kohl
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Mao
authors.forename: Debra
authors.initials: D
authors.lastname: McLoughlin
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Miller-Stein
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Rodman
authors.forename: Keith W
authors.initials: KW
authors.lastname: Rickert
authors.forename: Laura
authors.initials: L
authors.lastname: Sepp-Lorenzino
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Shipman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Thomas
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Wong
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
mesh_terms: D000818:Animals; D004285:Dogs; D008253:Macaca mulatta; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D040301:Vascular Endothelial Growth Factor Receptor-2