title: Identification of potent and selective VEGFR receptor tyrosine kinase inhibitors having new amide isostere headgroups.
abstract: A novel series of malonamide-type dual VEGFR2/c-Met inhibitors in which one of the amide bonds was replaced by an amide isostere-a trifluoroethylamine unit, was designed, synthesized, and evaluated for their enzymatic and cellular inhibition of VEGFR2 and c-Met enzymes. Optimization of these molecular entities resulted in identification of potent and selective inhibitors of VEGFR2 enzyme.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc, 7220 rue Frederick-Banting, Montréal, QC, Canada H4S 2A1.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gaudette
authors.forename: Stéphane
authors.initials: S
authors.lastname: Raeppel
authors.forename: Hannah
authors.initials: H
authors.lastname: Nguyen
authors.forename: Normand
authors.initials: N
authors.lastname: Beaulieu
authors.forename: Carole
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupont
authors.forename: A Robert
authors.initials: AR
authors.lastname: Macleod
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2