Synthesis of oxadiazolidinedione derivatives as quisqualic acid analogues and their evaluation at a quisqualate-sensitized site in the rat hippocampus.
The ability of quisqualic acid (1) to sensitize neurons to depolarization by omega-phosphono alpha-amino acid analogues of excitatory amino acids is a highly specific phenomenon and is termed the QUIS effect. In an attempt to elucidate the structure-activity relationships for this sensitization, analogues 2-6 of quisqualic acid have been synthesized. Compounds 4, 5, and 6 showed no quisqualate sensitization with respect to L-2-amino-6-phosphonohexanoic acid (L-AP6), while compounds 2 and 3 were 1/10 and 1/1000, respectively, as active as quisqualic acid in sensitizing neurons toward L-AP6.
Department of Medicinal Chemistry, College of Pharmacy, Medical School, University of Minnesota, Minneapolis 55455.
S
S
Venkatraman
R J
RJ
Roon
M K
MK
Schulte
J F
JF
Koerner
R L
RL
Johnson
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010069:Oxadiazoles / Q000737:chemistry*; D016318:Quisqualic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D010069:Oxadiazoles; D016318:Quisqualic Acid