Identification of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the management of cough and anxiety

A series of nortropane analogs based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. The synthesis and structure–activity relationships around the C-3 nortropane substitution are described. From the SAR study and hPXR screening effort, compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.

Graphical abstractA series of 3-disubstituted-nortropane analogs have been identified to bind to the nociceptin receptor with high affinity. The syntheses and structure–activity relationships of these analogs are described. Compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.Figure optionsDownload full-size imageDownload as PowerPoint slide