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

A novel series of monoamine reuptake inhibitors, the 1-amino-3-(1 H-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.