Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists

被引：44

作者：

Ahmed, M

Briggs, MA

Bromidge, SM

Buck, T

Campbell, L

Deeks, NJ

Garner, A

Gordon, L

Hamprecht, DW

Holland, V

Johnson, CN

Medhurst, AD

Mitchell, DJ

Moss, SF

Powles, J

Seal, JT

Stean, TO

Stemp, G

Thompson, M

Trail, B

Upton, N

Winborn, K

Witty, DR

机构：

[1] GlaxoSmithKline Inc, Neurol & GI Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

[2] GlaxoSmithKline Inc, Psychiat Ctr Excellence Drug Discovery, Harlow CM19 5AW, Essex, England

[3] GlaxoSmithKline Inc, Discovery Res, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 21期

关键词：

D O I：

10.1016/j.bmcl.2005.06.107

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4867 / 4871

页数：5