Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: identification of a lead and initial SAR studies.
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.
Lavey
Brian J
BJ
Department of Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-1-1545, Kenilworth, NJ 07033-0539, USA. brian.lavey@spcorp.com
Kozlowski
Joseph A
JA
Hipkin
R William
RW
Gonsiorek
Waldemar
W
Lundell
Daniel J
DJ
Piwinski
John J
JJ
Narula
Satwant
S
Lunn
Charles A
CA
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
D000577:Amides; D002186:Cannabinoids; D008024:Ligands; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D013450:Sulfones; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014508:Urea