Novel sulfamoyl benzamides as selective CB(2) agonists with improved in vitro metabolic stability

Bioorg Med Chem Lett. 2010 Jan 1;20(1):387-91. doi: 10.1016/j.bmcl.2009.10.062. Epub 2009 Oct 17.

Abstract

A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB(2) agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB(2) receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB(2) agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry*
  • Aniline Compounds / pharmacokinetics
  • Animals
  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacokinetics
  • Humans
  • Microsomes, Liver / metabolism
  • Pain / drug therapy
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB2 / agonists*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacokinetics

Substances

  • Aniline Compounds
  • Benzamides
  • N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide
  • Receptor, Cannabinoid, CB2
  • Sulfonamides