Abstract
We have developed versatile methods toward the synthesis of a variety of piperidine/piperazine bridged isosteres of pridopidine. The compounds were assessed against the D2 receptor in agonist and antagonist modes and against the D4 receptor in agonist mode. hERG Binding and the ADME profiles were studied.
Keywords:
C-arylation; Constrained amines; Dopaminergic activity; Oxabicyclic piperazines; Oxabicyclic piperidines.
Copyright © 2018 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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Bridged Bicyclo Compounds / chemical synthesis
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Bridged Bicyclo Compounds / chemistry
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Bridged Bicyclo Compounds / pharmacology
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Crystallography, X-Ray
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Dopamine Antagonists / chemical synthesis
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Dopamine Antagonists / chemistry
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Dopamine Antagonists / pharmacology
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Drug Design*
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ERG1 Potassium Channel / metabolism
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Humans
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Magnetic Resonance Spectroscopy
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Mice
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Piperazine / chemical synthesis
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Piperazine / chemistry*
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Piperazine / pharmacology
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacology
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D4 / agonists
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Receptors, Dopamine D4 / antagonists & inhibitors
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Structure-Activity Relationship
Substances
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Bridged Bicyclo Compounds
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DRD2 protein, human
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DRD4 protein, human
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Dopamine Antagonists
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ERG1 Potassium Channel
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KCNH2 protein, human
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Piperidines
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Receptors, Dopamine D2
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Receptors, Dopamine D4
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Piperazine
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piperidine