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

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.
Callain Y Kim 1,  Paige E Mahaney,  Oliver McConnell,  Yingru Zhang,  Eric Manas,  Douglas M Ho,  Darlene C Deecher,  Eugene J Trybulski
Affiliations

Affiliation

  • 1 Chemical Sciences, Wyeth Research, Arcola Road, Collegeville, PA 19426, USA. [email protected]
PMID: 19632110 DOI: 10.1016/j.bmcl.2009.07.053
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.

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