N-Glycine-sulfonamides as potent dual orexin 1/orexin 2 receptor antagonists

被引：28

作者：

Aissaoui, Hamed ^{[1
,2
]}

Koberstein, Ralf ^{[1
,2
]}

Zumbrunn, Cornelia ^{[1
,2
]}

Gatfield, John ^{[1
,2
]}

Brisbare-Roch, Catherine ^{[2
]}

Jenck, Francois ^{[2
]}

Treiber, Alexander ^{[2
]}

Boss, Christoph ^{[1
,2
]}

机构：

[1] Actel Pharmaceut Ltd, CH-4123 Basel, Switzerland

[2] Actel Pharmaceut Ltd, CH-4123 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 21期

关键词：

Orexin; Dual orexin antagonist; N-Glycine-sulfonamide; Oral bioavailability; Brain penetration;

D O I：

10.1016/j.bmcl.2008.09.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

A series of dual OX(1)R/OX(2)R orexin antagonists was prepared based on a N-glycine-sulfonamide core. SAR studies of a screening hit led to compounds with low nanomolar affinity for both receptors and good oral bioavailability. One of these compounds, 47, has demonstrated in vivo activity in rats following oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5729 / 5733

页数：5

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