title: Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: identification of a lead and initial SAR studies.
abstract: A novel class of cannabinoid CB2 receptor ligands is described. These triaryl bis-sulfones are nanomolar inhibitors of the CB2 receptor and show high selectivity over the cannabinoid CB1 receptor. One example of this new class decreases ligand-induced GTPgammaS binding to recombinant CB2 cell membranes, identifying the compound as a CB2-selective inverse agonist.
authors.affiliation: Department of Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-1-1545, Kenilworth, NJ 07033-0539, USA. brian.lavey@spcorp.com
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: R William
authors.initials: RW
authors.lastname: Hipkin
authors.forename: Waldemar
authors.initials: W
authors.lastname: Gonsiorek
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundell
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Satwant
authors.initials: S
authors.lastname: Narula
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lunn
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D002186:Cannabinoids; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D013450:Sulfones; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014508:Urea