1,4-dihydro-2,3-quinoxalinediones as potential flavin metabolites and excitatory amino acid receptor ligands. Part 1: Synthesis and pharmacological evaluation of the benzylic oxidation series of 1,4-dihydro-6,7-dimethyl-2,3-quinoxalinedione.
A series of five 6,7-disubstituted 1,4-dihydro-2,3-quinoxalinediones was prepared, two of which are known microbial flavin metabolites and three of which are potential flavin metabolites. Four of the five compounds inhibited specific binding of [3H]-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic acid ([3H]AMPA), [3H]kainic acid, and [3H]6-cyano-1,4-dihydro-7-nitro-2,3-quinoxalinedione ([3H]CNQX) in rat brain homogenate fractions, with IC50 values in the low micromolar range (the fifth compound competed only with [3H]CNQX). Two of the compounds were moderately potent AMPA antagonists in an in vitro functional test.
Bhat
A
A
Department of Molecular Pharmacology, School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470, USA.
Chang
H M
HM
Wallace
L J
LJ
Weinstein
D M
DM
Shams
G
G
Garris
C C
CC
Hill
R A
RA
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005415:Flavins / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D013329:Structure-Activity Relationship
D018691:Excitatory Amino Acid Antagonists; D005415:Flavins; D008024:Ligands; D011810:Quinoxalines; D017470:Receptors, Glutamate