NR2B subtype-selective NMDA receptor antagonists: 2001 – 2004

Abstract

Discovery of the NR2A – D subtypes of the N-methyl-D-aspartate (NMDA) receptor, and of an allosteric binding site on the NR2B receptor subunit, has renewed interest in the therapeutic potential of NMDA receptor antagonists. Many previous clinical efforts with non-selective NMDA antagonists have failed due to unacceptable CNS side effects. NMDA antagonists that selectively bind to the NR2B subunit, however, have demonstrated a larger therapeutic window in animal models of a number of disease states. In the last few years, there has been a significant increase in the structural diversity of small-molecule NR2B-selective NMDA antagonists. This review will focus on patents and patent applications published from 2001 to 2004 and will divide compounds into the three general classes of phenols, phenol replacements and non-phenols, with further subdivisions within these classes.

• CNS
• glutamate
• ion-channel
• NMDA
• NR2B antagonist