Non-aromatic A-ring replacement in the triaryl bis-sulfone CB2 receptor inhibitors

The triaryl bis-sulfone 1 was modified by converting the aryl A-ring to a piperidine ring. The piperidine ring was further elaborated to a spirocyclopropyl piperidine moiety. The effect on CB2 binding potency, rat calcium channel affinity, and CYP 2C9 inhibition is described.

A-ring replacements of 1 were investigated leading to compound 53 which had good affinity for the human CB2 receptor, reduced affinity for the rat calcium channel, and an improved cytochrome P450 profile.Figure optionsDownload as PowerPoint slide