Novel sulfamoyl benzamides as selective CB2 agonists with improved in vitro metabolic stability

A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB2 agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB2 receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB2 agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.

Graphical abstractThe discovery and SAR studies of a series of xylene sulfonamides as CB2 selective agonists are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide