- Discovery of 3,9-diazabicyclo[4.2.1]nonanes as potent dual orexin receptor antagonists with sleep-promoting activity in the rat.
Discovery of 3,9-diazabicyclo[4.2.1]nonanes as potent dual orexin receptor antagonists with sleep-promoting activity in the rat.
Bioorganic & medicinal chemistry letters (2010-07-09)
Paul J Coleman, John D Schreier, Anthony J Roecker, Swati P Mercer, Georgia B McGaughey, Christopher D Cox, George D Hartman, C Meacham Harrell, Duane R Reiss, Scott M Doran, Susan L Garson, Wayne B Anderson, Cuyue Tang, Thomayant Prueksaritanont, Christopher J Winrow, John J Renger
PMID20610153
ABSTRACT
Orexins are excitatory neuropeptides that regulate arousal and sleep. Orexin receptor antagonists promote sleep and offer potential as a new therapy for the treatment of insomnia. In this Letter, we describe the synthesis of constrained diazepanes having a 3,9 diazabicyclo[4.2.1]nonane bicyclic core with good oral bioavailability and sleep-promoting activity in a rat EEG model.