Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases.
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.
Claridge
Stephen
S
Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1. claridges@methylgene.com
Raeppel
Franck
F
Granger
Marie-Claude
MC
Bernstein
Naomy
N
Saavedra
Oscar
O
Zhan
Lijie
L
Llewellyn
David
D
Wahhab
Amal
A
Deziel
Robert
R
Rahil
Jubrail
J
Beaulieu
Normand
N
Nguyen
Hannah
H
Dupont
Isabelle
I
Barsalou
Annie
A
Beaulieu
Carole
C
Chute
Ian
I
Gravel
Serge
S
Robert
Marie-France
MF
Lefebvre
Sylvain
S
Dubay
Marja
M
Pascal
Roussen
R
Gillespie
Jeff
J
Jin
Zhiyun
Z
Wang
James
J
Besterman
Jeffrey M
JM
MacLeod
A Robert
AR
Vaisburg
Arkadii
A
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
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2