title: Evaluation of indazole-based compounds as a new class of potent KDR/VEGFR-2 inhibitors.
abstract: A novel class of potent and selective inhibitors of KDR incorporating an indazole moiety 1 is reported. The discovery, synthesis, and structure-activity relationships of this series of inhibitors have been investigated. The most promising compounds were also profiled to determine their pharmacokinetic properties and evaluated in a VEGF-induced vascular permeability assay.
authors.affiliation: Department of Medicinal Chemistry, Amgen, Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bauer
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Whittington
authors.forename: Angela
authors.initials: A
authors.lastname: Coxon
authors.forename: James
authors.initials: J
authors.lastname: Bready
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Harriman
authors.forename: Vinod F
authors.initials: VF
authors.lastname: Patel
authors.forename: Anthony
authors.initials: A
authors.lastname: Polverino
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Harmange
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011485:Protein Binding / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2