Orexin receptor antagonists: Medicinal chemistry and therapeutic potential

被引：79

作者：

Roecker, Anthony J. ^{[1
]}

Coleman, Paul J. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2008年 / 8卷 / 11期

关键词：

orexin; hypocretin; insomnia; almorexant; GPCR; cataplexy; OX1R; OX2R;

D O I：

10.2174/156802608784936746

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Actelion Pharmaceuticals achieved clinical proof-of-concept for the treatment of insomnia in 2007 with the release of Phase II data on Almorexant, a potent dual (OX1R/OX2R) orexin receptor antagonist. GlaxoSmithKline also released clinical efficacy data on an orexin receptor antagonist in 2007 for the treatment of insomnia. With these exciting findings, the search for orexin ( or hypocretin) receptor antagonists for the treatment of sleep and neurological disorders has recently increased in intensity in the pharmaceutical industry. This review will focus on the medicinal chemistry of orexin antagonists and the potential therapeutic value of this therapy for the treatment of insomnia. Receptor subtype selectivity will also be described to highlight the tools currently available to delineate receptor-specific pharmacology.

引用

页码：977 / 987

页数：11

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