Discovery of Spiropiperidine-Based Potent and Selective Orexin-2 Receptor Antagonists.

Abstract 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).