4-fluorosulfonylpiperidines:: Selective 5-HT2A ligands for the treatment of insomnia

被引：31

作者：

Fish, LR

Gilligan, MT

Humphries, AC

Ivarsson, M

Ladduwahetty, T

Merchant, KJ

O'Connor, D

Patel, S

Philipps, E

Vargas, HM

Hutson, PH

MacLeod, AM

机构：

[1] Merck Sharp & Dohme Ltd, Neurosci Res Ctr, Harlow CM20 2QR, Essex, England

[2] Safety Assessment, Dept Pharmacol Sci, West Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 16期

关键词：

D O I：

10.1016/j.bmcl.2005.05.104

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Incorporation of fluorine at the 4-position of an existing series of sulfonyl piperidine 5-HT2A antagonists gave compounds with increased selectivity over the IKr potassium channel. This work led to the identification of 3b, a compound that gave no increase in QT(c) in the anesthetized dog up to plasma levels as high as 148 mu M. Furthermore, 3b has been shown to increase slow-wave sleep bout duration and to decrease the number of awakenings in rats, indicating the potential utility of 5-HT2A antagonists in the treatment of insomnia. (c) 2005 Elsevier Ltd. All rights reserved.

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收藏

页码：3665 / 3669

页数：5

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