Rational Design, Synthesis and Pharmacological Evaluation of the (2R)- and (2S)-Stereoisomers of 3-(2-Carboxypyrrolidinyl)-2-methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors.

Julie Rasmussen, Morten Storgaard, Darryl S Pickering, Lennart Bunch

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    7 Citations (Scopus)

    Abstract

    In this paper we describe the rational design, synthesis and pharmacological evaluation of two new stereoisomeric (S)-glutamate (Glu) analogues. The rational design was based on hybrid structures of the natural product kainic acid, a synthetic analogue CPAA and the high-affinity Glu analogue SYM2081. Pharmacological evaluation of the two stereoisomers revealed that one stereoisomer showed a subtype selectivity profile with low micromolar affinity for GluK1 and GluK3 and a 10- to 15-fold lower affinity for GluK2. The other stereoisomer displayed full selectivity for the KA over AMPA and NMDA receptors (GluK1-3: 0.39, 0.51 and 0.099¿µM, respectively).
    Original languageEnglish
    JournalChemMedChem
    Volume6
    Issue number3
    Pages (from-to)498-504
    Number of pages7
    ISSN1860-7179
    DOIs
    Publication statusPublished - 7 Mar 2011

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