Stereoselective synthesis and preliminary evaluation of new D-3-heteroarylcarbonylalanines as ligands of the NMDA receptor.
New N-heteroarylcarbonylalanines of the D-series were stereoselectively prepared from enoates derived from D-mannitol. These compounds were active in binding and functional assays of the NMDA sub-type of glutamate receptors. A pyridine derivative inhibited MK801 binding, protected neurons from excitotoxic damage and blocked NMDA-induced currents in neurons. A thiophene derivative positively modulated the NMDA receptor, possibly through the allosteric glycine site.
Lima
Paulo G
PG
Laboratório de Química Bioorgânica, Núcleo de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Bloco J, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
Caruso
Rodrigo R B
RR
Alves
Simone O
SO
Pessôa
Renata F
RF
Mendonça-Silva
Dayde L
DL
Nunes
Ricardo J
RJ
Noël
François
F
Castro
Newton G
NG
Costa
Paulo R R
PR
D000409:Alanine / Q000138:chemical synthesis* / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013237:Stereoisomerism; D013876:Thiophenes / Q000138:chemical synthesis / Q000378:metabolism
D008024:Ligands; D016194:Receptors, N-Methyl-D-Aspartate; D013876:Thiophenes; D016291:Dizocilpine Maleate; D000409:Alanine