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.
2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Alkanes / chemistry
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Alkanes / pharmacokinetics
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Alkanes / pharmacology*
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Animals
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Aza Compounds / chemistry
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Aza Compounds / pharmacokinetics
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Aza Compounds / pharmacology
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Biological Availability
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Bridged Bicyclo Compounds / chemistry
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Bridged Bicyclo Compounds / pharmacokinetics
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Bridged Bicyclo Compounds / pharmacology
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Drug Discovery*
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Electroencephalography
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Hypnotics and Sedatives / chemistry
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Hypnotics and Sedatives / pharmacokinetics
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Hypnotics and Sedatives / pharmacology*
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Orexin Receptors
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Rats
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Rats, Sprague-Dawley
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Receptors, Neuropeptide / antagonists & inhibitors*
Substances
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Alkanes
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Aza Compounds
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Bridged Bicyclo Compounds
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Hypnotics and Sedatives
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Orexin Receptors
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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nonane