2. Academic Validation
  3. Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors

Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors

  • Bioorg Med Chem Lett. 2009 Oct 1;19(19):5807-10. doi: 10.1016/j.bmcl.2009.07.050.
Paige E Mahaney 1,  Callain Y Kim,  Richard D Coghlan,  Stephen T Cohn,  Gavin D Heffernan,  Christine A Huselton,  Eugene A Terefenko,  An T Vu,  Puwen Zhang,  Kevin D Burroughs,  Scott A Cosmi,  Jenifer A Bray,  Grace H Johnston,  Darlene C Deecher,  Eugene J Trybulski
Affiliations

Affiliation

  • 1 Chemical Sciences, Wyeth Research, Collegeville, PA 19426, United States. [email protected]
PMID: 19713106 DOI: 10.1016/j.bmcl.2009.07.050
Abstract

The SAR of a series of 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols as monoamine reuptake inhibitors, with a goal to improve both potency toward inhibiting the norepinephrine transporter and selectivity over the Serotonin Transporter, is reported. The effect of specific substitution on both the 3-phenyl group and the indole moiety were explored. This study led to the discovery of compound 20 which inhibited the norepinephrine transporter with an IC50 value of 4 nM while exhibiting 86-fold selectivity over the Serotonin Transporter.

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