Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

Research output: Contribution to journalJournal articleResearchpeer-review

  • Paola Conti
  • Marco De Amici
  • Samuele Joppolo Di Ventimiglia
  • Tine B Stensbøl
  • Madsen, Ulf
  • Bräuner, Hans
  • Emilio Russo
  • Giovambattista De Sarro
  • Giuseppe Bruno
  • Carlo De Micheli
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.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume46
Issue number14
Pages (from-to)3102-8
ISSN0022-2623
DOIs
Publication statusPublished - 3 Jul 2003

    Research areas

  • Amino Acids, Acidic, Amino Acids, Dicarboxylic, Animals, Anticonvulsants, CHO Cells, Cerebral Cortex, Cricetinae, Crystallography, X-Ray, Dicarboxylic Acids, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Heterocyclic Compounds, 2-Ring, Isoxazoles, Male, Mice, Mice, Inbred DBA, Molecular Conformation, Rats, Receptors, Metabotropic Glutamate, Receptors, N-Methyl-D-Aspartate, Stereoisomerism

ID: 45596619