Tricyclic heteroaromatic systems. 3-substituted 1,2,3,5,6,7-hexahydro-2,5,6-trioxopyrazino[1,2,3-de]-quinoxalines as novel antagonists at the glycine-NMDA site.
Two novel antagonists of the glycine-NMDA receptor have been synthesized and tested for their ability to displace [3H]glycine from its specific binding site in rat brain cortical membranes. The 3-substituted pyrazino[1,2,3-de]quinoxalin-2,5,6-triones 1a-b contain all the essential pharmacophoric descriptors of a glycine receptor antagonist. A model is proposed for the binding of these compounds that includes some of the interactions postulated for the potent glycine-NMDA receptor antagonist L-689,560.
Varano
F
F
Dipartimento di Scienze Farmaceutiche, Università di Firenze, Italy.
Catarzi
D
D
Colotta
V
V
Cecchi
L
L
Filacchioni
G
G
Galli
A
A
Costagli
C
C
D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000634:Aminoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D005998:Glycine