Abstract
The discovery and synthesis of a series of (dimethoxyphenoxy)alkylamino acetamides as orexin-2 receptor antagonists from a small-molecule combinatorial library using a high-throughput calcium mobilization functional assay (HEK293-human OX2-R cell line) is described. Active compounds show a good correlation between high-throughput single concentration screening data and measured IC(50)s. Specific examples exhibit IC(50) values of approximately 20 nM using human orexin A as the peptide agonist for the orexin-2 receptor.
MeSH terms
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Acetamides / chemical synthesis*
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Acetamides / chemistry
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Calcium / chemistry
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Cell Line
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Chemistry, Pharmaceutical / methods*
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Combinatorial Chemistry Techniques
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Drug Design
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Humans
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Inhibitory Concentration 50
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Intracellular Signaling Peptides and Proteins / chemistry*
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Models, Chemical
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Mutation
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Neuropeptides / chemistry*
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled / antagonists & inhibitors*
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Receptors, Neuropeptide / antagonists & inhibitors*
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Temperature
Substances
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Acetamides
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HCRT protein, human
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Intracellular Signaling Peptides and Proteins
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Neuropeptides
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Calcium