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

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 value 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.