Scaffold hopping, synthesis and structure–activity relationships of 5,6-diaryl-pyrazine-2-amide derivatives: A novel series of CB1 receptor antagonists

A scaffold hopping approach has been exploited to design a novel class of cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis of shape-complementarity and synthetic feasibility the central fragment, a methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1 antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide derivatives are described. Several compounds showed antagonist potency below 10 nM for the CB1 receptor.

Using a shape-based scaffold hopping approach a novel class of cannabinoid (CB1) receptor antagonists has been identified, which incorporate a six-membered pyrazine ring instead of the five-membered methylpyrazole as central fragment.Figure optionsDownload as PowerPoint slide