Synthesis and Biological Characterization of 3-Substituted 1H-Indoles as Ligands of GluN2B-Containing N-Methyl-d-aspartate Receptors. Part 2

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• 作者：Rosaria Gitto ; Laura De Luca ; Stefania Ferro ; Maria R. Buemi ; Emilio Russo ; Giovambattista De Sarro ; Mariangela Chisari ; Lucia Ciranna ; Alba Chimirri
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：December 13, 2012
• 年：2012
• 卷：55
• 期：23
• 页码：10532-10539
• 全文大小：363K
• 年卷期：v.55,no.23(December 13, 2012)
• ISSN：1520-4804

文摘

In the course of the identification of new indole derivatives targeting GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptor, the (N-1H-indol-6-methanesulfonamide-3-yl)-2-(4-benzylpiperidin-1-yl)ethanone (10b) was identified as a potent ligand for this NMDA receptor subunit. It displays very high binding affinity (IC₅₀ of 8.9 nmol) for displacement of [³H]ifenprodil, thus showing improved potency with respect to the previously reported analogues as confirmed by functional assay. This finding was consistent with the docking pose of compound 10b within the binding pocket localized in the GluN1-GluN2B subunit interface of NMDA receptor tetraheteromeric complex.