Synthesis of Oxadiazolidinedione Derivatives as Quisqualic Acid Analogs 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, ana...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1994-11, Vol.37 (23), p.3939-3946
Main Authors: Venkatraman, Shankar, Roon, Robert J., Schulte, Marvin K., Koerner, James F., Johnson, Rodney L.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chemistry
Exact sciences and technology
Glutamatergic system (aspartate and other excitatory aminoacids)
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Hippocampus - drug effects
Hippocampus - metabolism
In Vitro Techniques
Male
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Organic chemistry
Oxadiazoles - chemistry
Pharmacology. Drug treatments
Preparations and properties
Quisqualic Acid - analogs & derivatives
Quisqualic Acid - chemical synthesis
Quisqualic Acid - pharmacology
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00049a013