Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

  • J Med Chem. 2003 Jul 3;46(14):3102-8. doi: 10.1021/jm0308085.
Paola Conti  1 ,  Marco De Amici ,  Samuele Joppolo Di Ventimiglia ,  Tine B Stensbøl ,  Ulf Madsen ,  Hans Bräuner-Osborne ,  Emilio Russo ,  Giovambattista De Sarro ,  Giuseppe Bruno ,  Carlo De Micheli
Affiliations
  • 1. Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Viale Abruzzi 42, 20131 Milano, Italy.
PMID: 12825948 DOI: 10.1021/jm0308085
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.