Abstract
Herein, we report the synthesis and structure-activity relationship of a novel series of (R)-4,4-difluoropiperidine core scaffold as dopamine receptor 4 (D4) antagonists. A series of compounds from this scaffold are highly potent against the D4 receptor and selective against the other dopamine receptors. In addition, we were able to confirm the active isomer as the (R)-enantiomer via an X-ray crystal structure.
Keywords:
Addiction; Difluoropiperidine; Dopamine 4 receptor; PD-LIDs; Selectivity.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antipsychotic Agents / chemical synthesis
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Antipsychotic Agents / chemistry*
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Antipsychotic Agents / pharmacokinetics
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Antipsychotic Agents / pharmacology*
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Crystallography, X-Ray
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Dopamine Antagonists / chemistry*
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Dopamine Antagonists / pharmacology*
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Drug Discovery
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Halogenation
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Humans
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Isomerism
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Models, Molecular
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Piperidines / chemistry*
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Piperidines / pharmacokinetics
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Piperidines / pharmacology*
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Rats
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Receptors, Dopamine D4 / antagonists & inhibitors*
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Receptors, Dopamine D4 / chemistry
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Receptors, Dopamine D4 / metabolism
Substances
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Antipsychotic Agents
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Dopamine Antagonists
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Piperidines
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Receptors, Dopamine D4