TY - JOUR
T1 - Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators
AU - Zimmerman, Sommer S.
AU - Khatri, Alpa
AU - Garnier-Amblard, Ethel C.
AU - Mullasseril, Praseeda
AU - Kurtkaya, Natalie L.
AU - Gyoneva, Stefka
AU - Hansen, Kasper B.
AU - Traynelis, Stephen F.
AU - Liotta, Dennis C.
PY - 2014/3/27
Y1 - 2014/3/27
N2 - NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca2+-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors.
AB - NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca2+-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors.
UR - https://www.scopus.com/pages/publications/84897425744
U2 - 10.1021/jm401695d
DO - 10.1021/jm401695d
M3 - Article
C2 - 24512267
AN - SCOPUS:84897425744
SN - 0022-2623
VL - 57
SP - 2334
EP - 2356
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 6
ER -