title: Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases.
abstract: A series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases is described. The compounds demonstrated potency with IC(50) values in the low nanomolar range in vitro while the lead compound also showed in vivo activity against various human tumor xenograft models in mice. Further exploration of this class of compounds is underway.
authors.affiliation: Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1. claridges@methylgene.com
authors.forename: Stephen
authors.initials: S
authors.lastname: Claridge
authors.forename: Franck
authors.initials: F
authors.lastname: Raeppel
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Granger
authors.forename: Naomy
authors.initials: N
authors.lastname: Bernstein
authors.forename: Oscar
authors.initials: O
authors.lastname: Saavedra
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhan
authors.forename: David
authors.initials: D
authors.lastname: Llewellyn
authors.forename: Amal
authors.initials: A
authors.lastname: Wahhab
authors.forename: Robert
authors.initials: R
authors.lastname: Deziel
authors.forename: Jubrail
authors.initials: J
authors.lastname: Rahil
authors.forename: Normand
authors.initials: N
authors.lastname: Beaulieu
authors.forename: Hannah
authors.initials: H
authors.lastname: Nguyen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dupont
authors.forename: Annie
authors.initials: A
authors.lastname: Barsalou
authors.forename: Carole
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Ian
authors.initials: I
authors.lastname: Chute
authors.forename: Serge
authors.initials: S
authors.lastname: Gravel
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: Roussen
authors.initials: R
authors.lastname: Pascal
authors.forename: Jeff
authors.initials: J
authors.lastname: Gillespie
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Jin
authors.forename: James
authors.initials: J
authors.lastname: Wang
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Besterman
authors.forename: A Robert
authors.initials: AR
authors.lastname: MacLeod
authors.forename: Arkadii
authors.initials: A
authors.lastname: Vaisburg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008956:Models, Chemical; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2