Substituted acyclic sulfonamides as human cannabinoid-1 receptor inverse agonists

Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.

Graphical abstractSulfonamide analogues of the potent CB1R inverse agonist 2 (Taranabant) were optimized for CB1R activity.Figure optionsDownload full-size imageDownload as PowerPoint slide