Abstract
Single enantiomer [(aryloxy)(pyridinyl)methyl]piperidine and pyrrolidine derivatives 5-9 are inhibitors of monoamine reuptake. Structure-activity relationships established that monoamine reuptake inhibition are functions of amine, pyridine isomer, aryloxy ring substitution and stereochemistry. Consequently, selective NRIs, selective SRIs, dual SNRIs and triple SNDRIs were all identified. Dual SNRIs 5l-a and 9c were evaluated in additional pharmacology and pharmacokinetic studies as representative examples from this series.
MeSH terms
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Adrenergic Uptake Inhibitors / chemical synthesis
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Adrenergic Uptake Inhibitors / chemistry*
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Adrenergic Uptake Inhibitors / pharmacokinetics
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Animals
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Drug Design
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Norepinephrine / metabolism*
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Piperidines / chemical synthesis
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Piperidines / chemistry*
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Piperidines / pharmacokinetics
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Pyrrolidines / chemical synthesis
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Pyrrolidines / chemistry*
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Pyrrolidines / pharmacokinetics
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Rats
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Selective Serotonin Reuptake Inhibitors / chemical synthesis
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Selective Serotonin Reuptake Inhibitors / chemistry*
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics
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Serotonin / metabolism
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Adrenergic Uptake Inhibitors
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Piperidines
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Pyrrolidines
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Serotonin Uptake Inhibitors
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Serotonin
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Norepinephrine