Trisubstituted sulfonamides: A new chemotype for development of potent and selective CB2 receptor inverse agonists

Article abstract of DOI:10.1021/ml3004236

An extensive exploration of the structure-activity relationship of a trisubstituted sulfonamide series led to the identification of 39, which is a potent and selective CB₂ receptor inverse agonist [K _i(CB₂) = 5.4 nM, and K_i(CB₁) = 500 nM]. The functional properties measured by cAMP assays indicated that the selected compounds were CB₂ inverse agonists with high potency values (for 34, EC₅₀ = 8.2 nM, and for 39, EC₅₀ = 2.5 nM). Furthermore, an osteoclastogenesis bioassay indicated that trisubstituted sulfonamide compounds showed great inhibition of osteoclast formation.