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.
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页码：1988 / 1992
页数：5
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