Novel 5-(benzyloxy)pyridin-2(1H)-one derivatives as potent c-Met inhibitors

Bioorg Med Chem Lett. 2013 Apr 15;23(8):2408-13. doi: 10.1016/j.bmcl.2013.02.037. Epub 2013 Feb 14.

Abstract

A series of novel 5-(benzyloxy)pyridin-2(1H)-ones were designed, synthesized and biologically evaluated for c-Met inhibition. Various amides and benzoimidazoles at C-3 position were investigated. A potent compound 12b with a c-Met IC50 of 12nM was identified. This compound exhibited potent inhibition of EBC-1 cell associated with c-Met constitutive activation and showed high selectivity for c-Met than other tested 11 kinases. The binding model 12b with c-Met was disclosed by docking analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Drug Design
  • Humans
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / chemistry
  • Pyridones / chemical synthesis
  • Pyridones / chemistry*
  • Pyridones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Protein Kinase Inhibitors
  • Pyridones
  • Proto-Oncogene Proteins c-met