Synthesis of C5-tetrazole derivatives of 2-amino-adipic acid displaying NMDA glutamate receptor antagonism.
Five derivatives of 2-amino-adipic acid bearing a tetrazole-substituted in C5 position were synthesized. These compounds displayed selective antagonism towards N-methyl-D: -aspartate (NMDA) receptors compared with AMPA receptors, and they were devoid of any neurotoxicity. Among these five analogues, one exhibited a higher affinity for synaptic NMDA responses than the other four. Therefore, C5 tetrazole-substituted of 2-amino-adipic acid represent an interesting series of new NMDA receptor antagonists. This approach may be considered as a new strategy to develop ligands specifically targeted to synaptic or extra-synaptic NMDA receptors.
Lenda
Fatimazohra
F
Institut des Biomolécules Max Mousseron UMR 5247 CNRS-Universités Montpellier 1 et 2, Université Montpellier 2, Pl. E. Bataillon, Montpellier Cedex 5, France.
Crouzin
Nadine
N
Cavalier
Mélanie
M
Guiramand
Janique
J
Lanté
Fabien
F
Barbanel
Gérard
G
Cohen-Solal
Catherine
C
Martinez
Jean
J
Guenoun
Farhate
F
Lamaty
Frédéric
F
Vignes
Michel
M
D000272:Adipates / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000272:Adipates; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C045574:1H-tetrazole; C029900:adipic acid