4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: design, synthesis and structure-activity relationships.

Article Details

Citation

Fish PV, Andrews MD, Jonathan Fray M, Stobie A, Wakenhut F, Whitlock GA

4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: design, synthesis and structure-activity relationships.

Bioorg Med Chem Lett. 2009 May 15;19(10):2829-34. doi: 10.1016/j.bmcl.2009.03.090. Epub 2009 Mar 26.

PubMed ID
19359175 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DuloxetineCytochrome P450 2D6IC 50 (nM)1000N/AN/ADetails
DuloxetineSodium-dependent dopamine transporterIC 50 (nM)590N/AN/ADetails
DuloxetineSodium-dependent noradrenaline transporterIC 50 (nM)5N/AN/ADetails
DuloxetineSodium-dependent serotonin transporterIC 50 (nM)4N/AN/ADetails