3-hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists.
The synthesis and Gly/NMDA, AMPA and KA receptor binding activities of some 3-hydroxy-quinazoline-2,4-dione derivatives are reported. The binding data, together with functional antagonism studies, showed that the 3-hydroxy-quinazoline-2,4-dione moiety can be considered a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. In fact, introduction of chlorine atom(s) on precise position(s) of the benzofused moiety yielded Gly/NMDA selective antagonists, while the presence of the 6-(1,2,4-triazol-4-yl) group shifted the affinity and selectivity towards the AMPA receptor.
Colotta
Vittoria
V
Dipartimento di Scienze Farmaceutiche, Universita' degli Studi di Firenze, Polo Scientifico, Via Ugo Schiff, 6, 50019 Sesto Fiorentino, (FI), Italy. vittoria.colotta@unifi.it
Catarzi
Daniela
D
Varano
Flavia
F
Calabri
Francesca Romana
FR
Filacchioni
Guido
G
Costagli
Chiara
C
Galli
Alessandro
A
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
C494078:3-hydroxy-quinazoline-2,4-dione; D018691:Excitatory Amino Acid Antagonists; D011799:Quinazolines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate