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

被引：13

作者：

Kim, Callain Y. ^{[1
]}

Mahaney, Paige E. ^{[1
]}

McConnell, Oliver ^{[1
]}

Zhang, Yingru ^{[1
]}

Manas, Eric ^{[1
]}

Ho, Douglas M. ^{[2
]}

Deecher, Darlene C. ^{[1
]}

Trybulski, Eugene J. ^{[1
]}

机构：

[1] Wyeth Res, Chem Sci, Collegeville, PA 19426 USA

[2] Princeton Univ, Dept Chem, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 17期

关键词：

Vasomotor symptoms; Monoamine reuptake inhibitor; Norepiephrine reuptake inhibitor; NRI; NE; 5-HT; ENANTIOMERIC SEPARATION; CHIRAL TECHNOLOGY; NOREPINEPHRINE; ANTIDEPRESSANT; REBOXETINE; EFFICACY;

D O I：

10.1016/j.bmcl.2009.07.053

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (IC50 = 28 nM) with excellent selectivity over the dopamine transporter and 13-fold selectivity over the serotonin transporter. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5029 / 5032

页数：4

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