Abstract
The synthesis and biological evaluation of novel cycloheptaquinoline antagonists of the human H(3) receptor are described. Two series of compounds, bearing either an amino substituent or an alkyne linker at the 11-position, were investigated. Modifications of the amino substituents, optimization of chain length and the effect of conformational restraints are described. Several compounds with high affinity and selectivity for the H(3) receptor were discovered.
MeSH terms
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Animals
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cloning, Molecular
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Drug Evaluation, Preclinical
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Histamine Antagonists / chemical synthesis*
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Histamine Antagonists / pharmacology*
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Humans
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Mass Spectrometry
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Molecular Conformation
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Quinolines / chemical synthesis*
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Quinolines / pharmacology*
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Rats
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Receptors, Histamine H1 / drug effects
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Receptors, Histamine H2 / drug effects
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Receptors, Histamine H3 / drug effects*
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Recombinant Proteins / chemistry
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Structure-Activity Relationship
Substances
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Histamine Antagonists
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Indicators and Reagents
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Quinolines
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Receptors, Histamine H1
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Receptors, Histamine H2
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Receptors, Histamine H3
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Recombinant Proteins