Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.

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Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA

Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors.

Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21.

PubMed ID
21093273 [ View in PubMed
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Abstract

The present work describes a series of novel chiral amines that potently inhibit the in vitro reuptake of serotonin, norepinephrine and dopamine (triple reuptake inhibitors) and were active in vivo in a mouse model predictive of antidepressant like activity. The detailed synthesis and in vitro activity and ADME profile of compounds is described, which represent a previously undisclosed triple reuptake inhibitor chemotype.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
FluoxetineSodium-dependent serotonin transporterIC 50 (nM)5.2N/AN/ADetails
NomifensineSodium-dependent dopamine transporterIC 50 (nM)30.2N/AN/ADetails
SertralineCytochrome P450 2C19IC 50 (nM)310N/AN/ADetails
SertralineCytochrome P450 2C9IC 50 (nM)>10000N/AN/ADetails
SertralineCytochrome P450 2D6IC 50 (nM)1400N/AN/ADetails
SertralineCytochrome P450 3A4IC 50 (nM)800N/AN/ADetails
SertralineSodium-dependent dopamine transporterIC 50 (nM)310N/AN/ADetails
SertralineSodium-dependent serotonin transporterIC 50 (nM)3N/AN/ADetails