Structure-activity relationships of chiral selective norepinephrine reuptake inhibitors (sNRI) with increased oxidative stability

被引：8

作者：

Hudson, Sarah ^{[1
]}

Kiankarimi, Mehrak ^{[1
]}

Eccles, Wendy ^{[1
]}

Dwight, Wesley ^{[1
]}

Mostofi, Yalda S. ^{[1
]}

Genicot, Marc J. ^{[1
]}

Fleck, Beth A. ^{[2
]}

Gogas, Kathleen ^{[3
]}

Aparicio, Anna ^{[4
]}

Wang, Hua ^{[4
]}

Wen, Jenny ^{[4
]}

Wade, Warren S. ^{[1
]}

机构：

[1] Neurocrine Biosci Inc, Dept Med Chem, San Diego, CA 92130 USA

[2] Neurocrine Biosci Inc, Dept Pharmacol, San Diego, CA 92130 USA

[3] Neurocrine Biosci Inc, Dept Neurosci, San Diego, CA 92130 USA

[4] Neurocrine Biosci Inc, Dept Preclin Dev, San Diego, CA 92130 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 16期

关键词：

norepinephrine; serotonin;

D O I：

10.1016/j.bmcl.2008.07.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and SAR of a series of chiral heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. The best compounds compare favorably with atomoxetine in potency (IC(50)s < 10 nM), selectivity against the other monoamine transporters, and inhibition of CYP2D6 (IC(50)s > 1 mu M). In addition, the compounds are generally more stable than atomoxetine to oxidative metabolism and thus are likely to have lower clearance in humans. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4491 / 4494

页数：4

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