Vittorino Servadio

Synthesis of a new series of N-hydroxy, N-alkylamides of aminoacids as ligands of NMDA glycine site

Abstract Anew series of N-hydroxy, N-alkylamides of aminoacids structurally related to the N-hydroxy-3-amino-2 pyrrolidone [(±)HA-966] was synthesised and evaluated for the ability to displace [ 3 H]Glycine, [ 3 H]CGS19755, [ 3 H]AMPA and [ 3 H]Kainate binding sites. The N-heptyl glycinamide 5a was the most potent compound (IC 50 = 4.5 μM) in inhibiting [ 3 H]Glycine binding. Compounds 5b , 5d , 5m , 5p , 5q and 5r showed an activity similar to (±)HA-966, whereas 5h , 5i , 5n and 5s appeared less active. None of the compounds tested exhibited a significant displacement of [ 3 H]AMPA and [ 3 H]Kainate binding sites. Compounds active in the [ 3 H]Glycine binding inhibited, to a different degree, NMDA induced contractions in guinea-pig LMPP preparation.