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Updated: Jul 8, 2026

Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
Proline bis-amides as potent dual orexin receptor antagonists
Jeffrey M Bergman1, Anthony J Roecker, Swati P Mercer
1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Abstract:
A series of OX(2)R/OX(1)R dual orexin antagonists was prepared based on a proline bis-amide identified as a screening lead. Through a combination of classical and library synthesis, potency enhancing replacements for both amide portions were discovered. N-methylation of the benzimidazole moiety within the lead structure significantly reduced P-gp susceptibility while increasing potency, giving rise to good brain penetration. A compound from this series has demonstrated in vivo central activity when dosed peripherally in a pharmacodynamic model of orexin activity.
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