Referenced in: none

Automatically associated channels: Slo1

Title: Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators.

Authors: Sommer S Zimmerman, Alpa Khatri, Ethel C Garnier-Amblard, Praseeda Mullasseril, Natalie L Kurtkaya, Stefka Gyoneva, Kasper B Hansen, Stephen F Traynelis, Dennis C Liotta

Journal, date & volume: J. Med. Chem., 2014 Mar 27 , 57, 2334-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24512267

Abstract
NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca(2+)-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.