6973-93-9Relevant articles and documents
Photochemically knocking out glutamate receptors in vivo
Chambers, James J.,Gouda, Hiroaki,Young, David M.,Kuntz, Irwin D.,England, Pamela M.
, p. 13886 - 13887 (2007/10/03)
AMPA (α-amino-3-hydroxy-5-methyl-4-isooxazole) receptors, a major subtype of ionotropic glutamate receptors (iGluRs), mediate the majority of the fast communication between neurons, and the activity-dependent trafficking of AMPA receptors at synapses plays a role in mammalian learning and memory. Here we describe the design, synthesis, and evaluation of a photoreactive AMPA receptor antagonist that provides a means of "knocking out" AMPA receptors present on the surface of cells. The antagonist, 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX), was designed by introducing a photoreactive azido group onto a quinoxalinedione inhibitor scaffold. Computational docking of ANQX to the AMPA receptor ligand-binding core predicted efficient binding to AMPA receptors. Glutamate-evoked currents were reversibly blocked at micromolar ANQX concentrations prior to photolysis and irreversibly blocked following photolysis. ANQX provides a means of directly evaluating the trafficking of native AMPA receptors with unparalleled spatiotemporal resolution. Copyright
Ytterbium triflate catalyzed heterocyclization of 1,2-phenylenediamines and alkyl oxalates under solvent-free conditions via phillips reaction: A facile synthesis of quinoxaline-2,3-diones derivatives
Wang, Limin,Liu, Jijun,Tian, He,Qian, Changtao
, p. 1349 - 1357 (2007/10/03)
Ytterbium triflate are found to catalyze efficiently the Phillips-type heterocyclization reactions of 1,2-phenylenediamine and alkyl oxalate under solvent-free and mild conditions to afford the corresponding quinoxaline-2,3-dione derivatives in high yields. The catalyst could be recovered almost quantitatively from the aqueous layer after the reaction was completed and it could be reused in subsequent reaction without decrease in activity.
Pyrrolylquinoxalinediones: A new class of AMPA receptor antagonists
Lubisch,Behl,Hofmann
, p. 2887 - 2892 (2007/10/03)
Pyrrolylquinoxalinediones were synthesized and their affinities for the AMPA receptor were determined. Most compounds showed moderate to good affinities. The acetic acid derivative 8b exhibited a K(i) value of 70 nM and was equipotent to NBQX 1. Structure activity relationships are discussed. Selected compounds were tested for their potency to inhibit AMPA induced lethal convulsions in mice. In this in vivo model the compounds showed improved potency compared with NBQX.
