Frølund Bente, Jensen Lars S, Storustovu Signe I, Stensbøl Tine B, Ebert Bjarke, Kehler Jan, Krogsgaard-Larsen Povl, Liljefors Tommy
Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
J Med Chem. 2007 Apr 19;50(8):1988-92. doi: 10.1021/jm070038n. Epub 2007 Mar 22.
A series of 4-aryl-5-(4-piperidyl)-3-isoxazolol GABAA 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 (Ki=10-70 nM) and antagonist potencies in the low nanomolar range (Ki=9-10 nM). These potencies are significantly higher than those of previously reported 4-PIOL antagonists and considerably higher than that of the standard GABAA antagonist SR 95531.
已合成了一系列4-芳基-5-(4-哌啶基)-3-异恶唑醇GABAA拮抗剂，并对其进行了药理学表征。间位苯基取代的化合物9k和9m以及对位苯氧基取代的化合物9l均显示出高亲和力（Ki = 10 - 70 nM），且在低纳摩尔范围内具有拮抗剂效力（Ki = 9 - 10 nM）。这些效力显著高于先前报道的4-PIOL拮抗剂，并且远高于标准GABAA拮抗剂SR 95531。
