纬-Aminobutyric Acid(C) (GABAC) Selective Antagonists Derived from the Bioisosteric Modification of 4-Aminocyclopent-1-enecarboxylic Acid: Amides and Hydroxamates

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• 作者：Katherine E. S. Locock ; Izumi Yamamoto ; Priscilla Tran ; Jane R. Hanrahan ; Mary Chebib ; Graham A. R. Johnston ; Robin D. Allan
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：July 11, 2013
• 年：2013
• 卷：56
• 期：13
• 页码：5626-5630
• 全文大小：276K
• 年卷期：v.56,no.13(July 11, 2013)
• ISSN：1520-4804

文摘

Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABA<sub>Csub>, the most potent being 4-ACPHA (10a, IC<sub>50sub> = 13 渭M) and 4-ACPAM (11a, IC<sub>50sub> = 10 渭M). This provides evidence that a zwitterionic structure is not essential for GABA<sub>Csub> antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding.