Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids

Paola Conti, 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

    32 Citationer (Scopus)

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

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