4-aryl-5-(4-piperidyl)-3-isoxazolol GABAA antagonists:: Synthesis, pharmacology, and structure-activity relationships

被引：34

作者：

Frolund, Bente ^{[1
]}

Jensen, Lars S.

Storustovu, Signe I.

Stensbol, Tine B.

Ebert, Bjarke

Kehler, Jan

Krogsgaard-Larsen, Povl

Liljefors, Tommy

机构：

[1] Univ Copenhagen, Fac Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark

[2] H Lundbeck & Co AS, Dept Mol Pharmacol Electrophysiol & Med Chem, DK-2500 Valby, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 08期

关键词：

D O I：

10.1021/jm070038n

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-aryl-5-(4-piperidyl)-3-isoxazolol GABA(A) antagonists have been synthesized and pharmacologically characterized. The meta-phenyl-substituted compounds 9k and 9m and the para-phenoxy-substituted compound 9l all display high affinities (K-i = 10-70 nM) and antagonist potencies in the low nanomolar range (K-i = 9-10 nM). These potencies are significantly higher than those of previously reported 4-PIOL antagonists and considerably higher than that of the standard GABA(A) antagonist SR 95531.

引用

页码：1988 / 1992

页数：5

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