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
  • 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.