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.
Synthesis and Anticonvulsant Activity of Novel Bicyclic Acidic Amino Acids / P. Conti, M. De Amici, S. Joppolo di Ventimiglia, T.B. Stensbol, U. Madsen, H. Bräuner-Osborne, E. Russo, G. De Sarro, G. Bruno, C. De Micheli. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 46:14(2003 May 29), pp. 3102-3108.
Synthesis and Anticonvulsant Activity of Novel Bicyclic Acidic Amino Acids
P. ContiPrimo
;M. De AmiciSecondo
;C. De MicheliUltimo
2003
Abstract
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.Pubblicazioni consigliate
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