Discovery of spiropiperidine-based potent and selective Orexin-2 receptor antagonists

To generate novel human Orexin-2 Receptor (OX2R) antagonists, a spiropiperidine based scaffold was designed and a SAR study was carried out. Compound 4f possessed the highest OX2R antagonistic activity with an IC50 value of 3 nM with 450-fold selectivity against Orexin-1 Receptor (OX1R).

To generate novel human Orexin-2 Receptor (OX2R) antagonists, a spiropiperidine based scaffold was designed and a SAR study was carried out. Compound 4f possessed the highest OX2R antagonistic activity with an IC50 value of 3 nM with 450-fold selectivity against Orexin-1 Receptor (OX1R).Figure optionsDownload as PowerPoint slide