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An extensive exploration of the SAR of a trisubstituted sulfonamides series led to the identification of 39 , which is a potent and selective CB 2 receptor inverse agonist (CB 2  K i = 5.4 nM, and CB 1  K i = 500 nM). The functional properties measured by cAMP assays indicated that the selected compounds were CB 2 inverse agonists with high potency values ( 34 , EC 50 = 8.2 nM, and 39 , EC 50 = 2.5 nM). Furthermore, an osteoclastogenesis bioassay indicated that trisubstituted sulfonamide compounds showed great inhibition of osteoclast formation.

Trisubstituted Sulfonamides: A New Chemotype for Development of Potent and Selective CB2 Receptor Inverse Agonists

Trisubstituted Sulfonamides: A New Chemotype for Development of Potent and Selective CB₂ Receptor Inverse Agonists