Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.

Basic Information

ID: ALA1144895

Journal: J Med Chem

Title: Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids.

Authors: Conti P, De Amici M, Joppolo Di Ventimiglia S, Stensbøl TB, Madsen U, Bräuner-Osborne H, Russo E, De Sarro G, Bruno G, De Micheli C.

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.

CiteXplore: 12825948

DOI: 10.1021/jm0308085

Patent ID: