Novel 4-(Piperidin-4-yl)-1-hydroxypyrazoles as γ-Aminobutyric AcidA Receptor Ligands: Synthesis, Pharmacology, and Structure−Activity Relationships

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• 作者：Henriette A. Mø ; ller ; Tommy Sander ; Jesper L. Kristensen ; Birgitte Nielsen ; Jacob Krall ; Marianne L. Bergmann ; Bolette Christiansen ; Thomas Balle ; Anders A. Jensen ; Bente Frø ; lund
• 刊名：Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：April 22, 2010
• 年：2010
• 卷：53
• 期：8
• 页码：3417-3421
• 全文大小：757K
• 年卷期：v.53,no.8(April 22, 2010)
• ISSN：1520-4804

文摘

A series of substituted 1-hydroxypyrazole analogues of the GABA_A receptor partial agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL) have been synthesized and pharmacologically characterized. Several of the analogues displayed K_i in the low nanomolar range at the native GABA_A receptors and potent antagonism of the α₁β₂γ₂ receptor. It appears that several regions situated in proximity to the core of the orthosteric binding site of the GABA_A receptor are able to accommodate large hydrophobic substituents.