Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593274 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
The orexin (or hypocretin) system has been identified as a novel target for the treatment of insomnia due to the wealth of biological and genetic data discovered over the past decade. Recently, clinical proof-of-concept was achieved for the treatment of primary insomnia using dual (OX1R/OX2R) orexin receptor antagonists. However, elucidation of the pharmacology associated with selective orexin-2 receptor antagonists (2-SORAs) has been hampered by the lack of orally bioavailable, highly selective small molecule probes. Herein, the discovery and optimization of a novel series of 2,5-diarylnicotinamides as potent and orally bioavailable orexin-2 receptor selective antagonists is described. A compound from this series demonstrated potent sleep promotion when dosed orally to EEG telemetrized rats.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Swati P. Mercer, Anthony J. Roecker, Susan Garson, Duane R. Reiss, C. Meacham Harrell, Kathy L. Murphy, Joseph G. Bruno, Rodney A. Bednar, Wei Lemaire, Donghui Cui, Tamara D. Cabalu, Cuyue Tang, Thomayant Prueksaritanont, George D. Hartman,