1056418-83-7Relevant articles and documents
Discovery of 2,5-diarylnicotinamides as selective orexin-2 receptor antagonists (2-SORAs)
Mercer, Swati P.,Roecker, Anthony J.,Garson, Susan,Reiss, Duane R.,Meacham Harrell,Murphy, Kathy L.,Bruno, Joseph G.,Bednar, Rodney A.,Lemaire, Wei,Cui, Donghui,Cabalu, Tamara D.,Tang, Cuyue,Prueksaritanont, Thomayant,Hartman, George D.,Young, Steven D.,Winrow, Christopher J.,Renger, John J.,Coleman, Paul J.
, p. 6620 - 6624 (2014/01/06)
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 (OX 1R/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.
