3,4-dihydro-2H-benzoxazinones are 5-HT1A receptor antagonists with potent 5-HT reuptake inhibitory activity

被引：56

作者：

Atkinson, PJ

Bromidge, SM

Duxon, MS

Gaster, LM

Hadley, MS

Hammond, B

Johnson, CN

Middlemiss, DN

North, SE

Price, GW

Rami, HK

Riley, GJ

Scott, CM

Shaw, TE

Starr, KR

Stemp, G

Thewlis, KM

Thomas, DR

Thompson, M

Vong, AKK

Watson, JM

机构：

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

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

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

[4] GlaxoSmithKline, Worldwide Bioanal DMPK, Harlow CM19 5AW, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 03期

关键词：

D O I：

10.1016/j.bmcl.2004.11.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from a high throughput screening hit, a series of 3,4-dihydro-2H-benzoxazinones has been identified with both high affinity for the 5-HT1A receptor and potent 5-HT reuptake inhibitory activity. The 5-(2-methyl)quinolinyloxy derivative combined high 5-HT1A/1B/1D receptor affinities with low intrinsic activity and potent inhibition of the 5-HT reuptake site (pK(i) 8.2). This compound also had good oral bioavailability and brain penetration in the rat. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：737 / 741

页数：5

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