Expansion of SAR studies on triaryl bis sulfone cannabinoid CB2 receptor ligands

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6785-9. doi: 10.1016/j.bmcl.2010.08.126. Epub 2010 Aug 31.

Abstract

We report further expansion of the structure activity relationship (SAR) on the triaryl bis sulfone class of compounds (I), which are potent CB(2) receptor ligands with excellent selectivity over the CB(1) receptor. This study was extended to B ring changes, followed by simultaneous optimization of the A-, B-, and C-rings. Compound 42 has excellent CB(2) potency, selectivity and rat exposure.

MeSH terms

  • Animals
  • Ligands
  • Rats
  • Receptor, Cannabinoid, CB2 / drug effects*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Structure-Activity Relationship
  • Sulfones / chemistry*
  • Sulfones / metabolism
  • Sulfones / pharmacology*

Substances

  • Ligands
  • Receptor, Cannabinoid, CB2
  • Sulfones