| Literature DB >> 19418500 |
David B Whitman1, Christopher D Cox, Michael J Breslin, Karen M Brashear, John D Schreier, Michael J Bogusky, Rodney A Bednar, Wei Lemaire, Joseph G Bruno, George D Hartman, Duane R Reiss, C Meacham Harrell, Richard L Kraus, Yuxing Li, Susan L Garson, Scott M Doran, Thomayant Prueksaritanont, Chunze Li, Christopher J Winrow, Kenneth S Koblan, John J Renger, Paul J Coleman.
Abstract
Silent Night: Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX(1)R/OX(2)R) orexin receptor antagonist featuring a 1,4-diazepane central constraint that blocks orexin signaling in vivo. In telemetry-implanted rats, oral administration of this antagonist produced a decrease in wakefulness, while increasing REM and non-REM sleep.Entities:
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Year: 2009 PMID： 19418500 DOI： 10.1002/cmdc.200900069
Source DB: PubMed Journal: ChemMedChem ISSN： 1860-7179 Impact factor: 3.466