Discovery of 2-[(2,4-dichlorophenyl)amino]-N-[(tetrahydro- 2H-pyran-4-yl)methyl]-4-(trifluoromethyl)- 5-pyrimidinecarboxamide, a selective CB2 receptor agonist for the treatment of inflammatory pain

J Med Chem. 2007 May 31;50(11):2597-600. doi: 10.1021/jm061195+. Epub 2007 May 4.

Abstract

Selective CB2 receptor agonists are promising potential therapeutic agents for the treatment of inflammatory and neuropathic pain. A focused screen identified a pyrimidine ester as a partial agonist at the CB2 receptor with micromolar potency. Subsequent lead optimization identified 35, GW842166X, as the optimal compound in the series. 35 has an oral ED50 of 0.1 mg/kg in the rat FCA model of inflammatory pain and was selected as a clinical candidate for this indication.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / pharmacokinetics
  • Analgesics / pharmacology
  • Animals
  • Biological Availability
  • Half-Life
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Pain / drug therapy*
  • Pain / metabolism
  • Pyrans / chemical synthesis*
  • Pyrans / pharmacokinetics
  • Pyrans / pharmacology
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / pharmacology
  • Rats
  • Receptor, Cannabinoid, CB2 / agonists*
  • Structure-Activity Relationship

Substances

  • 2-((2,4-dichlorphenyl)amino)-N-((tetrahydro-2H-pyran-4-yl)methyl)-4-(trifluoromethyl)-5-pyrimidinecarboxamide
  • Analgesics
  • Pyrans
  • Pyrimidines
  • Receptor, Cannabinoid, CB2