Synthesis and biological evaluation of new derivatives of 2-substituted 4-hydroxybutanamides as GABA uptake inhibitors

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• 作者：Katarzyna Kulig ; Krzysztof Wię ; ckowski ; Anna Wię ; ckowska ; Justyna Gajda ; Bartł ; omiej Pochwat ; Georg C. Hö ; fner ; Klaus T. Wanner ; Barbara Malawska
• 关键词：GABA-uptake inhibitors ; GAT1– ; 4 ; Butanamides
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：January 2011
• 年：2011
• 卷：46
• 期：1
• 页码：183-190
• 全文大小：260 K

文摘

This study presents the synthesis of novel substituted 4-hydroxybutanamides and their influence on the activity of murine GABA transport proteins GAT1–GAT4. The active compounds, derivatives of N-arylalkyl-2-(4-diphenylmethylpiperazin-1-yl)-4-hydroxybutyramide, are characterized by pIC₅₀ values in range of 3.92–5.06 and by slight subtype-selectivity. Among them N-4-chlorobenzylamide was the most potent GAT inhibitor (mGAT3), while N-benzylamide was the most active in GAT1-binding assay (pK_i = 4.96). The results pointed out that benzhydryl and benzylamide moieties are crucial for the activity of this class of compounds as murine GAT inhibitors.