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. Epub 2009 Jan 27.

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.

Publication types

  • Comparative Study

MeSH terms

  • Amides / chemistry*
  • Amides / pharmacology
  • Animals
  • Cell Line, Tumor
  • HCT116 Cells
  • Humans
  • Imidazolidines / chemistry*
  • Imidazolidines / pharmacology
  • Mice
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-met / administration & dosage*
  • Rats
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • Amides
  • Imidazolidines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-2