Discovery of S-777469: an orally available CB2 agonist as an antipruritic agent

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2803-6. doi: 10.1016/j.bmcl.2012.02.072. Epub 2012 Mar 3.

Abstract

The discovery of novel CB2 ligands based on the 3-carbamoyl-2-pyridone derivatives by adjusting the size of side chain at 1-, 5- and 6-position is reported. The structure-activity relationship around this template lead to the identification of S-777469 as a selective CB2 receptor agonist, which exhibited the significant inhibition of scratching induced by Compound 48/80 at 1.0 mg/kg po and 10 mg/kg po (55% and 61%, respectively).

MeSH terms

  • Administration, Oral
  • Animals
  • Antipruritics / administration & dosage
  • Antipruritics / chemistry*
  • Antipruritics / pharmacology*
  • CHO Cells
  • Cricetinae
  • Disease Models, Animal
  • Inhibitory Concentration 50
  • Ligands
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • Protein Binding / drug effects
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Receptor, Cannabinoid, CB2 / agonists*

Substances

  • Antipruritics
  • Ligands
  • Pyridones
  • Receptor, Cannabinoid, CB2
  • S-777469