2-Substituted 4-hydroxybutanamides as potential inhibitors of ¦Ã-aminobutyric acid transporters mGAT1-mGAT4: Synthesis and biological evaluation

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• 作者：Paula Kowalczyk ; Kinga Sa?at ; Georg C. H?fner ; Natalia Guzior ; Barbara Filipek ; Klaus T. Wanner ; Katarzyna Kulig
• 关键词：GABA uptake inhibitors ; GAT1-4 ; Butanamides ; Paw licking response ; Stretching behavior ; Motor deficits
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：21
• 期：17
• 页码：5154-5167
• 全文大小：1101 K

文摘

A series of 2-substituted 4-hydroxybutanamide derivatives has been synthesized by the aminolysis of appropriate 2-substituted dihydrofuran-2(3H)-one derivatives with various substituted benzylamines. The final compounds have been evaluated for their capability of inhibiting the GABA transport proteins GAT1-4 stably expressed in HEK-239 cell lines. The pIC₅₀ values determined were in the range 4.21-5.14. Two compounds (16a and 16d), which displayed the most interesting profiles in in vitro tests, have also been subjected to further preliminary behavioral studies, evaluating their antinociceptive activity in hot-plate, writhing, and formalin tests. Their influence on motor coordination has also been assessed.