Selectivity profiling of novel indene H1-antihistamines for the treatment of insomnia

被引：14

作者：

Li, Bin-Feng ^{[1
]}

Moree, Wilna J. ^{[1
]}

Yu, Jinghua ^{[1
]}

Coon, Timothy ^{[1
]}

Zamani-Kord, Said ^{[1
]}

Malany, Siobhan ^{[1
]}

Jalali, Kayvon ^{[1
]}

Wen, Jianyun ^{[1
]}

Wang, Hua ^{[1
]}

Yang, Chun ^{[1
]}

Hoare, Samuel R. J. ^{[1
]}

Petroski, Robert E. ^{[1
]}

Madan, Ajay ^{[1
]}

Crowe, Paul D. ^{[1
]}

Beaton, Graham ^{[1
]}

机构：

[1] Neurocrine Biosci, San Diego, CA 92130 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 08期

关键词：

H-1; receptor; H-1-antihistamine; Insomnia; Indene; Histamine; SAR; RECEPTOR ANTAGONISTS; CHLORPHENIRAMINE; DIPHENHYDRAMINE; DIMETHINDENE; TERFENADINE; METOPROLOL; SEDATION; DRUGS;

D O I：

10.1016/j.bmcl.2010.02.055

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of indene analogs of the H-1-antihistamine (-)-R-dimethindene was evaluated for selectivity in the search for potentially improved sedative-hypnotics. Variation of the 6-substitutent in the indene core in combination with a pendant electron rich heterocycle led to the identification of several potent H-1-antihistamines with desirable selectivity over CYP enzymes, the M-1 muscarinic receptor and the hERG channel. These compounds were candidates for further ADME profiling and in vivo evaluation. (C) 2010 Elsevier Ltd. All rights reserved.

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收藏

页码：2629 / 2633

页数：5

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