Delta agonist hydroxy bioisosteres: The discovery of 3-((1-benzylpiperidin-4-yl){4-[(diethylamino)carbonyl]phenyl}amino)benzamide with improved delta agonist activity and in vitro metabolic stability

被引：8

作者：

Griffin, Andrew M. ^{[1
]}

Brown, William ^{[1
]}

Walpole, Christopher ^{[1
]}

Coupal, Martin ^{[2
]}

Adam, Lynda ^{[2
]}

Gosselin, Mylene ^{[2
]}

Salois, Dominic ^{[2
]}

Morin, Pierre-Emmanuel ^{[2
]}

Roumi, Marie ^{[2
]}

机构：

[1] AstraZeneca R&D, Dept Med Chem, St Laurent, PQ H4S 1Z9, Canada

[2] AstraZeneca R&D, Dept Vitro Biol & DMPK, St Laurent, PQ H4S 1Z9, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 21期

关键词：

Delta agonism; Bioisosteres; Metabolic stability; PALLADIUM-CATALYZED AMINATION; OPIOID RECEPTORS; ARYL HALIDES; ANALOGS; DERIVATIVES; POTENT; PAIN;

D O I：

10.1016/j.bmcl.2009.09.068

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as improved in vitro metabolic stability. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5999 / 6003

页数：5

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