Discovery of novel c-Met inhibitors bearing a 3-carboxyl piperidin-2-one scaffold

Molecules. 2014 Feb 24;19(2):2655-73. doi: 10.3390/molecules19022655.

Abstract

A series of compounds containing a novel 3-carboxypiperidin-2-one scaffold based on the lead structure BMS-777607 were designed, synthesized and evaluated for their c-Met kinase inhibition and cytotoxicity against MKN45 cancer cell lines. The results indicated that five compounds exhibited significant inhibitory effect on c-Met with IC50 values of 8.6-81 nM and four compounds showed potent inhibitory activity against MKN45 cell proliferation, with IC50s ranging from 0.57-16 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / chemical synthesis
  • Aminopyridines / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Design
  • Humans
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / pharmacology*
  • 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
  • Structure-Activity Relationship

Substances

  • Aminopyridines
  • N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyridones
  • Proto-Oncogene Proteins c-met