Synthesis, glycine/NMDA and AMPA binding activity of some new 2,5,6-trioxopyrazino[1,2,3-de]quinoxalines and of their restricted analogs 2,5-dioxo- and 4,5-dioxoimidazo[1,5,4-de]quinoxalines.
The synthesis of some new 1,2,3,5,6, 7-hexahydro-2,5,6-trioxopyrazino[1,2,3-de]quinoxalines 1c-g and of their restricted analogs 2,4,5,6-tetrahydro-2,5-dioxo-1H- 2a-g and 5,6-dihydro-4,5-dioxo-4H-imidazo[1,5,4-de]quinoxalines 3a-d is reported. Compounds 1c-g, 2a-g, and 3a-d were tested for their binding activity at the glycine/NMDA and AMPA receptors. The results show that only the 6,6,6-tricyclic derivatives 1c-g are able to bind to the glycine/NMDA and AMPA receptors, although with lower affinity than the previously reported lead compounds 1a-b. In contrast, the 5,6,6-tricyclic derivatives 2a-g are inactive at both receptors and only one 4,5-dioxoimidazoquinoxaline (3b) displays a weak glycine/NMDA receptor affinity.
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
D000818:Animals; D008297:Male; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D018009:Receptors, Glycine / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013329:Structure-Activity Relationship
D011810:Quinoxalines; D018091:Receptors, AMPA; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate