4-Piperidines and 3-pyrrolidines as dual serotonin and noradrenaline reuptake inhibitors: design, synthesis and structure-activity relationships.
Article Details
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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
Drug Target Property Measurement pH Temperature (°C) Duloxetine Cytochrome P450 2D6 IC 50 (nM) 1000 N/A N/A Details Duloxetine Sodium-dependent dopamine transporter IC 50 (nM) 590 N/A N/A Details Duloxetine Sodium-dependent noradrenaline transporter IC 50 (nM) 5 N/A N/A Details Duloxetine Sodium-dependent serotonin transporter IC 50 (nM) 4 N/A N/A Details