Bicyclic acidic amino acids (±)-6 and (±)-7, which are conformationally constrained homologues of glutamic acid, were prepared via a strategy based on a 1,3-dipolar cycloaddition. The new amino acids were tested toward ionotropic and metabotropic glutamate receptor subtypes; both of them behaved as antagonists at mGluR1,5 and as agonists at mGluR2. Furthermore, whereas (±)-6 was inactive at all ionotropic glutamate receptors, (±)-7 displayed a quite potent antagonism at the NMDA receptors. In the in vivo tests on DBA/2 mice, the compounds displayed an anticonvulsant activity. The interesting pharmacological profile of (±)-7 qualifies it as a lead of novel neuroprotective agents.
|Titolo:||Synthesis and Anticonvulsant Activity of Novel Bicyclic Acidic Amino Acids|
|Autori interni:||DE AMICI, MARCO (Secondo)|
CONTI, PAOLA (Primo)
DE MICHELI, CARLO (Ultimo)
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||29-mag-2003|
|Digital Object Identifier (DOI):||10.1021/jm0308085|
|Appare nelle tipologie:||01 - Articolo su periodico|
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