Design, synthesis, and pharmacological evaluation of azetedine and pyrrolidine derivatives as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists

被引：14

作者：

Pettersson, Martin ^{[1
]}

Campbell, Brian M. ^{[1
]}

Dounay, Amy B. ^{[1
]}

Gray, David L. ^{[1
]}

Xie, Longfei ^{[1
]}

O'Donnell, Christopher J. ^{[1
]}

Stratman, Nancy C. ^{[1
]}

Zoski, Kim ^{[1
]}

Drummond, Elena ^{[1
]}

Bora, Gary ^{[1
]}

Probert, Al ^{[1
]}

Whisman, Tammy ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 02期

关键词：

Norepinephrine reuptake inhibitor; 5-HT1A agonist; NRI; NET; DAT; SERT; ADHD; Depression; EFFICACY; REBOXETINE;

D O I：

10.1016/j.bmcl.2010.11.066

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds with combined norepinephrine reuptake inhibitor (NRI) and serotonin 1A (5-HT1A) partial agonist pharmacology may offer a new therapeutic approach for treating symptoms of neuropsychiatric disorders including ADHD, depression, and anxiety. Herein we describe the design and optimization of novel chemical matter that exhibits favorable dual NRI and 5-HT1A partial agonist activity. Lead compounds in this series were found to be devoid of activity at the dopamine transporter and were shown to be brain penetrant with high receptor occupancy. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：865 / 868

页数：4

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