New Insomnia Treatment

  • Author: Scott Williams
  • Published Date: 05 March 2012
  • Source / Publisher: ChemMedChem/Wiley-VCH
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Insomnia and related sleep disorders have significant consequences on health and well-being. A lack of sleep impairs next-day function, and the incidence of sleep disorders increases with age. Orexin-secreting neurons that project from the hypothalamus stimulate wakefulness. The function of these excitatory neuropeptides was discovered through genetic studies on narcoleptic dogs and transgenic mice, linking dysfunction of this system with excessive sleepiness. Orexin antagonists induce sleep by selectively blocking wake-promoting signals, and this concept has been shown to have utility in clinical studies with orexin antagonists.


Paul Coleman and colleagues, Merck Research Laboratories, West Point, Pennsylvania, USA, report the design and synthesis of a potent dual orexin receptor antagonist (DORA) MK-6096. Analysis of the stereoelectronic properties of α-methyl piperidine carboxamides was used to design 2,5-disubstituted piperidine carboxamides with axially oriented substituents. MK-6096 is currently in phase II clinical studies.


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Magazine of Chemistry Europe (16 European Chemical Societies)published by Wiley-VCH