Orexin receptor antagonists: a review of promising compounds patented since 2006.
BACKGROUND
The orexin neuropeptide system plays a central role in maintaining arousal and wakefulness. It has been demonstrated that small molecule antagonists to the orexin receptors promote sleep in preclinical species and in patients with insomnia.


METHODS
This review provides a summary of published patent applications claiming novel orexin antagonists from 2006 to mid-2009, covering both selective and dual orexin receptor antagonists.


RESULTS
Readers will gain an overview of orexin biology focusing on genetic and pharmacological validation of this target for treating sleep disorders. Additionally, this review discusses the importance of receptor subtype selectivity and the potential role of subtype selective and dual orexin antagonists in treating psychiatric illnesses beyond insomnia. This review identifies companies that are significant contributors to the patent literature claiming novel orexin receptor antagonists.


CONCLUSIONS
The study of the orexin system has emerged as one of the key new fields of investigation in neuroscience. The demonstration of clinical proof-of-concept for the treatment of primary insomnia by Actelion in early 2007 has spurred significant interest in this field and competition has markedly increased since 2006.
Coleman
Paul J
PJ
Departments of Medicinal Chemistry and Neurology, Merck Research Laboratories, West Point, PA 19486, USA. paul_coleman@merck.com
Renger
John J
JJ
D000818:Animals; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D001523:Mental Disorders / Q000188:drug therapy / Q000503:physiopathology; D064446:Orexin Receptors; D010330:Patents as Topic; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology
D006993:Hypnotics and Sedatives; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide