Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT₆ receptor antagonists

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• 作者：Mahmood Ahmed ; Michael A. Briggs ; Steven M. Bromidge ; Tania Buck ; Lorraine Campbell ; Nigel J. Deeks ; Ashley Garner ; Laurie Gordon ; Dieter W. Hamprecht ; Vicky Holland et al.
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：2005
• 卷：15
• 期：21
• 页码：4867-4871
• 文件大小：260 K

摘要

Starting from the potent and selective but poorly brain penetrant 5-HT₆ receptor antagonist SB-271046, a successful strategy for improving brain penetration was adopted involving conformational constraint with concomitant reduction in hydrogen bond count. This provided a series of bicyclic heteroarylpiperazines with high 5-HT₆ receptor affinity. 5-Chloroindole 699929 combined high 5-HT₆ receptor affinity with excellent brain penetration and also had good oral bioavailability in both rat and dog.