Synthesis and Anticonvulsant Activity of Novel Bicyclic Acidic Amino Acids

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.