Abstract
The discovery and characterization of a novel chemical series of phosphorothioyl-containing imidazopyridines as potent neuropeptide S receptor antagonists is presented. The synthesis of analogues and their structure-activity relationship with respect to the Gq, Gs, and ERK pathways is detailed. The pharmacokinetics and in vivo efficacy of a potent analogue in a food intake rodent model are also included, underscoring its potential therapeutic value for the treatment of sleep, anxiety, and addiction disorders.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Drug Discovery
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Humans
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Imidazoles / chemistry*
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Imidazoles / pharmacokinetics
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Imidazoles / pharmacology*
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Mice
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Models, Molecular
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Molecular Conformation
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Neuropeptides / metabolism
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Receptors, Neuropeptide / antagonists & inhibitors*
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Receptors, Neuropeptide / metabolism
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Signal Transduction / drug effects
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Structure-Activity Relationship
Substances
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Imidazoles
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Neuropeptides
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Receptors, Neuropeptide
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neuropeptide S, human