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

摘要

An extensive exploration of the structure-activity relationship of a trisubstituted sulfonamide series led to the identi?cation of 39, which is a potent and selective CB2 receptor inverse agonist [Ki (CB2) = 5.4 nM, and Ki (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.