Abstract
The discovery of the CNS-penetrant and selective alpha(2C) adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure-activity studies demonstrate the structural requirements for binding affinity, functional activity, and selectivity over other alpha(2)-AR subtypes.
MeSH terms
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Adrenergic alpha-2 Receptor Antagonists*
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Animals
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Azepines / chemical synthesis*
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Azepines / pharmacology
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Brain / metabolism
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Central Nervous System / drug effects
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Cerebrospinal Fluid / metabolism
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Chemistry, Pharmaceutical / methods
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Drug Design
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Humans
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Kinetics
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Male
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Molecular Conformation
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Niacinamide / analogs & derivatives*
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Niacinamide / chemical synthesis*
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Niacinamide / pharmacology
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Rats
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Rats, Inbred WKY
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Receptors, Adrenergic, alpha-2 / chemistry
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Structure-Activity Relationship
Substances
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Adrenergic alpha-2 Receptor Antagonists
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Azepines
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N-(2-(4-(2,3-dihydrobenzo(1,4)dioxin-2-ylmethyl)-(1,4)diazepan-2-yl)ethyl)-2-phenoxynicotinamide
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Receptors, Adrenergic, alpha-2
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Niacinamide