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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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; Bunch, Lennart.
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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TY - JOUR
T1 - 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.
AU - Rasmussen, Julie
AU - Storgaard, Morten
AU - Pickering, Darryl S
AU - Bunch, Lennart
PY - 2011/3/7
Y1 - 2011/3/7
N2 - 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).
AB - 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).
U2 - 10.1002/cmdc.201000543
DO - 10.1002/cmdc.201000543
M3 - Journal article
C2 - 21268287
VL - 6
SP - 498
EP - 504
JO - Farmaco
JF - Farmaco
SN - 1860-7179
IS - 3
ER -
ID: 32927619