1. The Quest for the Best Dual Orexin Receptor Antagonist (Daridorexant) for the Treatment of Insomnia Disorders.
- Author
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Boss C, Gatfield J, Brotschi C, Heidmann B, Sifferlen T, von Raumer M, Schmidt G, Williams JT, Treiber A, and Roch C
- Subjects
- Dose-Response Relationship, Drug, Humans, Imidazoles chemistry, Molecular Structure, Orexin Receptor Antagonists chemistry, Pyrrolidines chemistry, Sleep Initiation and Maintenance Disorders metabolism, Imidazoles pharmacology, Orexin Receptor Antagonists pharmacology, Orexin Receptors metabolism, Pyrrolidines pharmacology, Sleep Initiation and Maintenance Disorders drug therapy
- Abstract
Since its discovery in 1998, the orexin system has been of interest to the research community as a potential therapeutic target for the treatment of sleep/wake disorders, stress and anxiety disorders, addiction or eating disorders. It consists of two G protein-coupled receptors, the orexin 1 and orexin 2 receptors, and two neuropeptides with agonistic effects, the orexin A and orexin B peptides. Herein we describe our efforts leading to the identification of a promising set of dual orexin receptor antagonists (DORAs) which subsequently went through physiology-based pharmacokinetic and pharmacodynamic modelling>
[1] and finally led to the selection of daridorexant, currently in phase 3 clinical trials for the treatment of insomnia disorders., (© 2020 Wiley-VCH GmbH.)- Published
- 2020
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