Abstract
A series of 3,3-disubstituted pyrrolidine monoamine triple reuptake inhibitors were discovered. Analogues with low nanomolar potency, good human in vitro microsomal stability and in vitro permeability, and low drug-drug interaction potential are described. One example showed in vivo anti-depressant-like effects in the mouse tail suspension assay with a minimum effective dose of 30 mg/kg i.p.
MeSH terms
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Animals
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Antidepressive Agents / pharmacology
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Dopamine Uptake Inhibitors / chemical synthesis*
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Dopamine Uptake Inhibitors / chemistry
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Dopamine Uptake Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Drug Design
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Humans
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Mice
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Molecular Structure
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Motor Activity / drug effects
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Norepinephrine / metabolism
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology*
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Serotonin / metabolism
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Tail / drug effects
Substances
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Antidepressive Agents
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Dopamine Uptake Inhibitors
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Pyrrolidines
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Serotonin
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Norepinephrine