Discovery of a new series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols.

Article Details

Citation

Kim CY, Mahaney PE, McConnell O, Zhang Y, Manas E, Ho DM, Deecher DC, Trybulski EJ

Discovery of a new series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols.

Bioorg Med Chem Lett. 2009 Sep 1;19(17):5029-32. doi: 10.1016/j.bmcl.2009.07.053. Epub 2009 Jul 23.

PubMed ID
19632110 [ View in PubMed
]
Abstract

A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols, have been discovered by combining virtual and focused screening efforts with design techniques. Synthesis of the two diastereomeric isomers of the molecule followed by chiral resolution of each enantiomer revealed the (2R,3S)-isomer to be a potent norepinephrine reuptake inhibitor (IC(50)=28 nM) with excellent selectivity over the dopamine transporter and 13-fold selectivity over the serotonin transporter.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DesipramineSodium-dependent noradrenaline transporterIC 50 (nM)3.4N/AN/ADetails
FluoxetineSodium-dependent serotonin transporterIC 50 (nM)9.4N/AN/ADetails