%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