title: N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: a novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors.
abstract: A series of N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides targeting c-Met and VEGFR2 tyrosine kinases was designed and synthesized. The compounds were potent against these two enzymes with IC(50) values in the low nanomolar range in vitro, possessed favorable pharmacokinetic profiles and showed high efficacy in vivo in several human tumor xenograft models in mice.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7220 rue Frederick-Banting, Montréal, QC, Canada H4S 2A1.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Raeppel
authors.forename: Stephen
authors.initials: S
authors.lastname: Claridge
authors.forename: Oscar
authors.initials: O
authors.lastname: Saavedra
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gaudette
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhan
authors.forename: Michael
authors.initials: M
authors.lastname: Mannion
authors.forename: Nancy
authors.initials: N
authors.lastname: Zhou
authors.forename: Franck
authors.initials: F
authors.lastname: Raeppel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Granger
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Isakovic
authors.forename: Robert
authors.initials: R
authors.lastname: Déziel
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: Marie-France
authors.initials: MF
authors.lastname: Robert
authors.forename: Sylvain
authors.initials: S
authors.lastname: Lefebvre
authors.forename: Marja
authors.initials: M
authors.lastname: Dubay
authors.forename: Jubrail
authors.initials: J
authors.lastname: Rahil
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.forename: Hélène
authors.initials: H
authors.lastname: Ste-Croix
authors.forename: A
authors.initials: A
authors.lastname: Robert Macleod
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Besterman
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D045325:HCT116 Cells; D006801:Humans; D048289:Imidazolidines / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000008:administration & dosage*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000577:Amides; D048289:Imidazolidines; D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2