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

  • Bioorg Med Chem Lett. 2009 Mar 1;19(5):1323-8. doi: 10.1016/j.bmcl.2009.01.068.
Stéphane Raeppel  1 ,  Stephen Claridge ,  Oscar Saavedra ,  Frédéric Gaudette ,  Lijie Zhan ,  Michael Mannion ,  Nancy Zhou ,  Franck Raeppel ,  Marie-Claude Granger ,  Ljubomir Isakovic ,  Robert Déziel ,  Hannah Nguyen ,  Normand Beaulieu ,  Carole Beaulieu ,  Isabelle Dupont ,  Marie-France Robert ,  Sylvain Lefebvre ,  Marja Dubay ,  Jubrail Rahil ,  James Wang ,  Hélène Ste-Croix ,  A Robert Macleod ,  Jeffrey Besterman ,  Arkadii Vaisburg
Affiliations
  • 1. Department of Medicinal Chemistry, MethylGene Inc., 7220 rue Frederick-Banting, Montréal, QC, Canada H4S 2A1.
PMID: 19211249 DOI: 10.1016/j.bmcl.2009.01.068
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.