Fig. 1.

A ligand-based pharmacophore model was derived by structure-activity relationship studies mapped to the GluN1/GluN2B structure. A, a homology model representing the full-length NMDA receptor is shown with ifenprodil bound. TMD, transmembrane domain; CTD, carboxyl-terminal domain. B, a detailed representation of ifenprodil within the binding cleft interface between the GluN1 and GluN2B ATD is shown. The features of the general pharmacophore model for GluN2B antagonists are highlighted; the cyan spheres represent the hydrophobic features of rings A and B. The hydrogen bond donors are shown in blue (amine of the linker region and hydroxyl of ring B) where as the hydrogen bond acceptor is shown as a red sphere. C, a representation of the ligand-based pharmacophore model derived for ifenprodil and related compounds with the same color scheme for pharmacophore features as in B.