Novel substituted 4-phenyl-[1,3]dioxanes:: potent and selective orexin receptor 2 (OX2R) antagonists

被引：61

作者：

McAtee, LC ^{[1
]}

Sutton, SW ^{[1
]}

Rudolph, DA ^{[1
]}

Li, XB ^{[1
]}

Aluisio, LE ^{[1
]}

Phuong, VK ^{[1
]}

Dvorak, CA ^{[1
]}

Lovenberg, TW ^{[1
]}

Carruthers, NI ^{[1
]}

Jones, TK ^{[1
]}

机构：

[1] Johnson & Johnson Res & Dev, LLC, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 16期

关键词：

D O I：

10.1016/j.bmcl.2004.06.032

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Orexins, also termed hypocretins, consist of two neuropeptide agonists (orexin A and B) interacting with two known G-protein coupled receptors (OX1R and OX2R). In addition to other biological functions, the orexin-2 receptor is thought to be an important modulator of sleep and wakefulness. Herein we describe a series of novel, selective OX2R antagonists consisting of substituted 4-phenyl-[1,3]dioxanes. One such antagonist is compound 9, 1-(2,4-dibromo-phenyl)-3-((4S,5s)-2,2-dimethyl-4-phenyl[1,3]dioxan-5-yl)-urea, which is bound by the OX2R with a pK(i) of 8.3, has a pK(b) of 7.9, and is 600-fold selective for the OX2R over the OX1R. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4225 / 4229

页数：5

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