N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases.
A family of thieno[3,2-b]pyridine based small molecule inhibitors of c-Met and VEGFR2 were designed based on lead structure 2. These compounds were shown to have IC(50) values in the low nanomolar range in vitro and were efficacious in human tumor xenograft models in mice in vivo.
Saavedra
Oscar
O
Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada H4S 2A1.
Claridge
Stephen
S
Zhan
Lijie
L
Raeppel
Franck
F
Granger
Marie-Claude
MC
Raeppel
Stéphane
S
Mannion
Michael
M
Gaudette
Frédéric
F
Zhou
Nancy
N
Isakovic
Ljubomir
L
Bernstein
Naomy
N
Déziel
Robert
R
Nguyen
Hannah
H
Beaulieu
Normand
N
Beaulieu
Carole
C
Dupont
Isabelle
I
Wang
James
J
Macleod
A Robert
AR
Besterman
Jeffrey M
JM
Vaisburg
Arkadii
A
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D006801:Humans; D008314:Malonates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D008314:Malonates; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C446540:thienopyridine; D019859:Proto-Oncogene Proteins c-met; D040301:Vascular Endothelial Growth Factor Receptor-2; C008314:malonamide