Characterization of Novel Selective H1-Antihistamines for Clinical Evaluation in the Treatment of Insomnia

被引：65

作者：

Moree, Wilna J. ^{[1
]}

Li, Bin-Feng ^{[1
]}

Jovic, Florence ^{[1
]}

Coon, Timothy ^{[1
]}

Yu, Jinghua ^{[1
]}

Gross, Raymond S. ^{[1
]}

Tucci, Fabio ^{[1
]}

Marinkovic, Dragan ^{[1
]}

Zamani-Kord, Said ^{[1
]}

Malany, Siobhan ^{[1
]}

Bradbury, Margaret J. ^{[1
]}

Hernandez, Lisa M. ^{[1
]}

O'Brien, Zhihong ^{[1
]}

Wen, Jianyun ^{[1
]}

Wang, Hua ^{[1
]}

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

Petroski, Robert E. ^{[1
]}

Sacaan, Aida ^{[1
]}

Madan, Ajay ^{[1
]}

Crowe, Paul D. ^{[1
]}

Beaton, Graham ^{[1
]}

机构：

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 17期

关键词：

RECEPTOR ANTAGONISTS; HEALTHY-VOLUNTEERS; DIMETHINDENE; HYPNOTICS; SLEEP; PHARMACOKINETICS; CHLORPHENIRAMINE; ENANTIOMERS; ZOLPIDEM; DOXEPIN;

D O I：

10.1021/jm900933k

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Analogues of the known H-1-antihistamine R-dimethindene were profiled as potential agents for the treatment of insomnia. Several highly selective compounds were efficacious in rodent sleep models. On the basis of overall profile, indene 1d and benzothiophene 2a had pharmacokinetic properties suitable for evaluation in night time dosing. Compound 2a did not show an in vivo cardiovascular effect from weak hERG channel inhibition.

引用

页码：5307 / 5310

页数：4

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