Triaryl bis-sulfones as cannabinoid-2 receptor ligands: SAR studies

We recently reported that compound 1 is a potent inhibitor of the CB2 receptor with high selectivity over CB1. This paper describes the SAR development for this class of compounds. Variation of the substitution pattern on the aromatic rings, as well as the groups linking them together, led to sub-nanomolar inhibitors of the CB2 receptor, with high selectivity over CB1.

Graphical abstractSAR studies on recently reported triaryl bis-sulfone cannabinoid CB2 receptor ligands are described. Modification of aryl substitution and their respective linkers gives compounds that are highly potent and selective for CB2. One compound is shown to be an orally available CB2-selective inverse agonist.Figure optionsDownload full-size imageDownload as PowerPoint slide