Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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.
OriginalsprogEngelsk
TidsskriftJournal of Medicinal Chemistry
Vol/bind46
Udgave nummer14
Sider (fra-til)3102-8
ISSN0022-2623
DOI
StatusUdgivet - 3 jul. 2003

ID: 45596619