Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: identification of a lead and initial SAR studies

Brian J Lavey; Joseph A Kozlowski; R William Hipkin; Waldemar Gonsiorek; Daniel J Lundell; John J Piwinski; Satwant Narula; Charles A Lunn

doi:10.1016/j.bmcl.2004.11.007

Triaryl bis-sulfones as a new class of cannabinoid CB2 receptor inhibitors: identification of a lead and initial SAR studies

Bioorg Med Chem Lett. 2005 Feb 1;15(3):783-6. doi: 10.1016/j.bmcl.2004.11.007.

Authors

Brian J Lavey¹, Joseph A Kozlowski, R William Hipkin, Waldemar Gonsiorek, Daniel J Lundell, John J Piwinski, Satwant Narula, Charles A Lunn

Affiliation

¹ Department of Chemistry, Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-1-1545, Kenilworth, NJ 07033-0539, USA. [email protected]

PMID: 15664857
DOI: 10.1016/j.bmcl.2004.11.007

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.

MeSH terms

Amides / chemistry
Amides / pharmacology
Cannabinoids / pharmacology
Cell Membrane / metabolism
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Humans
Ligands
Receptor, Cannabinoid, CB2 / antagonists & inhibitors*
Structure-Activity Relationship
Sulfonamides / chemistry
Sulfonamides / pharmacology
Sulfones / chemical synthesis*
Sulfones / pharmacology*
Urea / chemistry
Urea / pharmacology

Substances

Amides
Cannabinoids
Ligands
Receptor, Cannabinoid, CB2
Sulfonamides
Sulfones
Guanosine 5'-O-(3-Thiotriphosphate)
Urea