Abstract
The structure-activity relationship and the synthesis of novel N-benzyl-N-(pyrrolidin-3-yl)carboxamides as dual serotonin (5-HT) and noradrenaline (NA) monoamine reuptake inhibitors are described. Compounds such as 18 exhibited dual 5-HT and NA reuptake inhibition, good selectivity over dopamine (DA) reuptake inhibition and drug-like physicochemical properties consistent with CNS target space. Compound 18 was selected for further preclinical evaluation.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Central Nervous System / drug effects
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Combinatorial Chemistry Techniques
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Cytochrome P-450 CYP2D6 Inhibitors
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Dogs
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Dopamine Uptake Inhibitors / pharmacology
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Drug Design
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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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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism
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Molecular Conformation
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Norepinephrine / analysis*
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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
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Serotonin / analysis*
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Structure-Activity Relationship
Substances
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Amides
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Cytochrome P-450 CYP2D6 Inhibitors
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Dopamine Uptake Inhibitors
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Pyrrolidines
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Serotonin Uptake Inhibitors
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Serotonin
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Norepinephrine