Abstract
Analogs of the dual orexin receptor antagonist filorexant were prepared. Replacement of the ether linkage proved highly sensitive toward modification with an acetylene linkage providing compounds with the best in vitro and in vivo potency profiles.
Keywords:
Antagonist; Insomnia; Orexin.
Copyright © 2014 Elsevier Ltd. All rights reserved.
MeSH terms
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Acetylene / chemistry*
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Animals
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Dose-Response Relationship, Drug
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Mice
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Mice, Knockout
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Molecular Structure
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Orexin Receptor Antagonists*
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Orexin Receptors / deficiency
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Orexin Receptors / metabolism
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Piperidines / chemical synthesis
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Piperidines / chemistry
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Piperidines / pharmacology*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
Substances
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Cd200r1 protein, mouse
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Hcrtr1 protein, mouse
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MK-6096
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Orexin Receptor Antagonists
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Orexin Receptors
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Piperidines
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Pyrimidines
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Acetylene