Discovery of a novel potent GABAB receptor agonist

被引：22

作者：

Xu, Feng ^{[1
]}

Peng, Ge ^{[1
]}

Phan, Thu ^{[1
]}

Dilip, Usha ^{[1
]}

Chen, Jian Lu ^{[1
]}

Chernov-Rogan, Tania ^{[1
]}

Zhang, Xuexiang ^{[1
]}

Grindstaff, Kent ^{[1
]}

Annamalai, Thamil ^{[1
]}

Koller, Kerry ^{[1
]}

Gallop, Mark A. ^{[1
]}

Wustrow, David J. ^{[1
]}

机构：

[1] XenoPort Inc, Santa Clara, CA 95051 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期

关键词：

GABAB; Baclofen; SAR; Palladium; Boronate; Functional potency; Pyridylmethyl ether; PHARMACOLOGICAL EVALUATION; PHOSPHINIC ACID; BACLOFEN; ANALOGS; REFLUX;

D O I：

10.1016/j.bmcl.2011.08.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity studies have led to a discovery of 3-(4-pyridyl)methyl ether derivative 9d that has 25- to 50-fold greater functional potency than R-baclofen at human and rodent GABA(B) receptors in vitro. Mouse hypothermia studies confirm that this compound crosses the blood-brain barrier and is approximately 50-fold more potent after systemic administration. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6582 / 6585

页数：4

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