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

doi:10.1002/cmdc.201000543

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

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 language	English
Journal	ChemMedChem
Volume	6
Issue number	3
Pages (from-to)	498-504
Number of pages	7
ISSN	1860-7179
DOIs	https://doi.org/10.1002/cmdc.201000543
Publication status	Published - 7 Mar 2011

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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. / Rasmussen, Julie; Storgaard, Morten; Pickering, Darryl S et al.

In: ChemMedChem, Vol. 6, No. 3, 07.03.2011, p. 498-504.

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

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