Abstract
To prepare thiol-reactive ifenprodil derivatives designed as potential probes for cysteine-substituted NR2B containing NMDA receptors, electrophilic centers were introduced in different areas of the ifenprodil structure. Intermediates and final compounds were evaluated by binding studies and by electrophysiology to determine the structural requirements for their selectivity. The reactive compounds were further tested for their stability and for their reactivity in model reactions; some were found suitable as structural probes to investigate the binding site and the docking mode of ifenprodil in the NR2B subunit.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic alpha-Antagonists / chemical synthesis
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Adrenergic alpha-Antagonists / pharmacology*
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Affinity Labels / chemistry*
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Animals
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Binding Sites
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Brain / drug effects*
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Brain / metabolism
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Cysteine / chemistry
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Electrophysiology
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Membrane Potentials / drug effects*
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Membrane Potentials / physiology
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Models, Chemical
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Piperidines / chemical synthesis
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Piperidines / pharmacology*
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Rats
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Structure-Activity Relationship
Substances
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Adrenergic alpha-Antagonists
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Affinity Labels
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NR2B NMDA receptor
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Piperidines
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Receptors, N-Methyl-D-Aspartate
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Cysteine
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ifenprodil