Synthesis and Anticonvulsant Activity of Novel Bicyclic Acidic Amino Acids

Journal of Medicinal Chemistry
2003.0

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.

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