Abstract
A series of N-benzyl-N-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-amine monoamine reuptake inhibitors are described. Selective dual 5-HT and NA reuptake inhibition was achieved, and analogues with weak CYP2D6 inhibition, good human in vitro metabolic stability and wide ligand selectivity, such as 12b, were identified.
MeSH terms
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Amines / chemistry
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Chemistry, Pharmaceutical / methods*
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Cytochrome P-450 CYP2D6 Inhibitors*
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Drug Design
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Ether-A-Go-Go Potassium Channels / chemistry
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Hepatocytes / drug effects
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Hepatocytes / metabolism
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Humans
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Inhibitory Concentration 50
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Ligands
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Microsomes / drug effects
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Microsomes / metabolism
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Models, Chemical
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Molecular Conformation
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Norepinephrine / antagonists & inhibitors*
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology
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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 / pharmacology
Substances
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Amines
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Cytochrome P-450 CYP2D6 Inhibitors
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Ether-A-Go-Go Potassium Channels
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KCNH1 protein, human
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Ligands
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Pyrrolidines
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Serotonin Uptake Inhibitors
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Norepinephrine