%0 Generic %A Strong, Katie L. %A Epplin, Matthew P. %A Bacsa, John %A Butch, Christopher J. %A Burger, Pieter B. %A Menaldino, David S. %A Traynelis, Stephen F. %A Liotta, Dennis C. %D 2017 %T The Structure–Activity Relationship of a Tetrahydroisoquinoline Class of N‑Methyl‑d‑Aspartate Receptor Modulators that Potentiates GluN2B-Containing N‑Methyl‑d‑Aspartate Receptors %U https://acs.figshare.com/articles/dataset/The_Structure_Activity_Relationship_of_a_Tetrahydroisoquinoline_Class_of_i_N_i_Methyl_d_Aspartate_Receptor_Modulators_that_Potentiates_GluN2B-Containing_i_N_i_Methyl_d_Aspartate_Receptors/5144152 %R 10.1021/acs.jmedchem.7b00239.s002 %2 https://acs.figshare.com/ndownloader/files/8754514 %K GluN 2C NMDARs %K GluN 2B subunit %K enantiomeric pairs %K Multiple compounds potentiate %K CIQ %K methoxy substituents %K GluN 2B receptors %K GluN 2B GluN 2B %K isopropoxy moiety %K isopropoxy-containing scaffold %K GluN 2B GluN 2C %K GluN 2C subunits %K 2D %K allosteric modulators %K allosteric NMDA receptor %K GluN 2C tetrahydroisoquinoline analogues %K submicromolar EC 50 values %K Tetrahydroisoquinoline Class %X We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ. The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ. Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist. Multiple compounds potentiate the response of NMDARs with submicromolar EC50 values. Analysis of enantiomeric pairs revealed that the S-(−) enantiomer is active at the GluN2B, GluN2C, and/or GluN2D subunits, whereas the R-(+) enantiomer is only active at GluN2C/D subunits. These results provide a starting point for the development of selective positive allosteric modulators for GluN2B-containing receptors. %I ACS Publications