Design and synthesis of orally bioavailable benzimidazoles as Raf kinase inhibitors

J Med Chem. 2008 Nov 27;51(22):7049-52. doi: 10.1021/jm801050k.

Abstract

A series of arylaminobenzimidazoles was designed and synthesized as Raf kinase inhibitors. Exploration of the structure-activity relationship resulted in compounds that are potent in vitro and show desirable in vivo properties.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology*
  • Biological Availability
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Female
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Structure, Tertiary
  • Stereoisomerism
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays
  • raf Kinases / antagonists & inhibitors*
  • raf Kinases / metabolism

Substances

  • Benzimidazoles
  • Protein Kinase Inhibitors
  • raf Kinases