Synthesis of a set of ethyl 1-carbamoyl-3-oxoquinoxaline-2-carboxylates and of their constrained analogue imidazo.
The synthesis and glycine/NMDA and AMPA receptor affinities of a set of ethyl (+/-) 1-N-carbamoyl-1,2,3,4-tetrahydro-3-oxoquinoxaline-2-carboxylates 1-11 and those of their constrained analogue (+/-) 1,2,3,3a,4,5-hexahydroimidazo[1,5-a]quinoxaline-1,3,4-triones 12-24 are reported. Compounds 1-11 bear a side-chain at position 1 which has been spatially constrained in compounds 12-24. Most of the reported tricyclic derivatives 12-24 showed glycine/NMDA binding activity comparable to that of their corresponding bicyclic analogues 1-11 providing further evidence that the spatial orientation of the side-chain is an important structural requirement for glycine/NMDA receptor antagonists.
Varano
F
F
Dipartimento di Scienze Farmaceutiche, Universita' di Firenze, Via G. Capponi, 9, 50121, Firenze, Italy.
Catarzi
D
D
Colotta
V
V
Cecchi
L
L
Filacchioni
G
G
Galli
A
A
Costagli
C
C
D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D011810:Quinoxalines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013570:Synaptic Membranes
D002264:Carboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D011810:Quinoxalines; D018091:Receptors, AMPA; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate