Abstract
New histamine H3 receptor antagonists were developed using an acetylene moiety as a replacement for the amide-oxime functionality of verongamine 5. Optimization of receptor binding was performed by following aliphatic Topliss tree guidelines. These new H3 ligands demonstrate excellent blood-brain barrier penetration.
MeSH terms
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Acetylene / analogs & derivatives*
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Acetylene / chemical synthesis*
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Acetylene / chemistry
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Acetylene / pharmacology
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Animals
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Binding, Competitive
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Drug Design
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Guinea Pigs
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Heart / innervation
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Histamine Antagonists / chemical synthesis*
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Histamine Antagonists / chemistry
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Histamine Antagonists / pharmacology
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Kinetics
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Models, Molecular
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Molecular Conformation
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Molecular Structure
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Oximes / chemistry
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Oximes / pharmacology*
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Receptors, Histamine H3 / drug effects
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Receptors, Histamine H3 / metabolism*
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Structure-Activity Relationship
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Synaptosomes / metabolism
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Tyrosine / analogs & derivatives*
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Tyrosine / chemical synthesis*
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Tyrosine / chemistry
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Tyrosine / pharmacology
Substances
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Histamine Antagonists
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Oximes
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Receptors, Histamine H3
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verongamine
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Tyrosine
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Acetylene