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

T Fujimoto, Y Tomata, J Kunitomo, M Hirozane…

Index: Fujimoto, Tatsuhiko; Tomata, Yoshihide; Kunitomo, Jun; Hirozane, Mariko; Marui, Shogo Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 21 p. 6409 - 6413

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Citation Number: 10

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 3nM with 450-fold selectivity against Orexin-1 Receptor (OX1R).