N-Glycine-sulfonamides as potent dual orexin 1/orexin 2 receptor antagonists

A series of dual OX1R/OX2R orexin antagonists was prepared based on a N-glycine-sulfonamide core. SAR studies of a screening hit led to compounds with low nanomolar affinity for both receptors and good oral bioavailability. One of these compounds, 47, has demonstrated in vivo activity in rats following oral administration.

Graphical abstractThe structure–activity relationship and the synthesis of novel N-glycine-sulfonamides as OX1R/OX2R dual orexin antagonists are described. Compound 47 exhibited good oral bioavailability and has demonstrated in vivo activity in rats following oral administration.Figure optionsDownload full-size imageDownload as PowerPoint slide