Abstract
A novel synthesis of 1-substituted tetrahydro-1H-3-benzazepines 4 is described. Starting with (2-bromophenyl)acetaldehyde acetal 5, the nitrostyrene 9 was prepared in three steps allowing the addition of various nucleophiles to yield the nitroacetals 10. The one-pot Zn/HCl reductive cyclization of the nitroacetals 10 provided the 3-benzazepines 4, which were investigated for their affinity to the phencyclidine binding site of the NMDA receptor. A one-atomic spacer between the 3-benzazepine system and the phenyl residue in position 1 seems to be favorable for high NMDA receptor binding. In this series the benzazepine 4l substituted with the conformationally restricted and H-bond accepting acetanilide substituent in position 1 displays the highest NMDA receptor affinity (K(i)=89 nM).
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzazepines / chemical synthesis*
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Benzazepines / metabolism*
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Benzazepines / pharmacology
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Binding Sites
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Cell Membrane / metabolism
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Cerebral Cortex / drug effects*
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Cerebral Cortex / metabolism
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Dizocilpine Maleate / pharmacology
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Enzyme Inhibitors / metabolism*
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Excitatory Amino Acid Antagonists / pharmacology
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Hydrogen Bonding
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Molecular Conformation
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Molecular Structure
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Phencyclidine / metabolism*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / drug effects*
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Structure-Activity Relationship
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Swine
Substances
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Benzazepines
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Receptors, N-Methyl-D-Aspartate
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Dizocilpine Maleate
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Phencyclidine