N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases

Oscar Saavedra; Stephen Claridge; Lijie Zhan; Franck Raeppel; Marie-Claude Granger; Stéphane Raeppel; Michael Mannion; Frédéric Gaudette; Nancy Zhou; Ljubomir Isakovic; Naomy Bernstein; Robert Déziel; Hannah Nguyen; Normand Beaulieu; Carole Beaulieu; Isabelle Dupont; James Wang; A Robert Macleod; Jeffrey M Besterman; Arkadii Vaisburg

doi:10.1016/j.bmcl.2009.10.095

N3-arylmalonamides: a new series of thieno[3,2-b]pyridine based inhibitors of c-Met and VEGFR2 tyrosine kinases

Bioorg Med Chem Lett. 2009 Dec 15;19(24):6836-9. doi: 10.1016/j.bmcl.2009.10.095. Epub 2009 Oct 25.

Affiliation

¹ Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada H4S 2A1.

PMID: 19896842
DOI: 10.1016/j.bmcl.2009.10.095

Abstract

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.

MeSH terms

Administration, Oral
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacokinetics
Cell Line, Tumor
Humans
Malonates / chemical synthesis
Malonates / chemistry*
Malonates / pharmacokinetics
Mice
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacokinetics
Proto-Oncogene Proteins c-met / antagonists & inhibitors*
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacokinetics
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Antineoplastic Agents
Malonates
Protein Kinase Inhibitors
Pyridines
thienopyridine
Proto-Oncogene Proteins c-met
Vascular Endothelial Growth Factor Receptor-2
malonamide