Optimization of triaryl bis-sulfones as cannabinoid-2 receptor ligands

Structure–activity relationship on our recently reported triaryl bis-sulfone class of cannabinoid-2 (CB2) receptor selective inverse agonists was explored. Modifications to the methane sulfonamide, substitutions to B and C phenyl rings, and replacements of the C-ring were investigated. A compound with excellent CB2 activity, selectivity for CB2 over CB1, and in vivo plasma levels was identified.

Graphical abstractOptimization of triaryl bis-sulfone cannabinoid ligands is described. Formation of the trifluoromethane sulfonamide moiety gives compounds that are highly potent and selective for CB2 with improved plasma levels.Figure optionsDownload full-size imageDownload as PowerPoint slide