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 Citationer (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).

Originalsprog	Engelsk
Tidsskrift	ChemMedChem
Vol/bind	6
Udgave nummer	3
Sider (fra-til)	498-504
Antal sider	7
ISSN	1860-7179
DOI	https://doi.org/10.1002/cmdc.201000543
Status	Udgivet - 7 mar. 2011

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10.1002/cmdc.201000543

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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.
I: ChemMedChem, Bind 6, Nr. 3, 07.03.2011, s. 498-504.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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). ",

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AU - Storgaard, Morten

AU - Pickering, Darryl S

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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.

Abstract

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