Rational Design, Synthesis and Pharmacological Evaluation of the (2 R )‐ and (2 S )‐Stereoisomers of 3‐(2‐Carboxypyrrolidinyl)‐2‐methyl Acetic Acid as Ligands for the Ionotropic Glutamate Receptors
| Autor: | Darryl S. Pickering, Lennart Bunch, Morten Storgaard, Julie L. Rasmussen |
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| Rok vydání: | 2011 |
| Předmět: |
Kainic acid
Stereochemistry Glutamic Acid Kainate receptor AMPA receptor Acetates Ligands Receptors Ionotropic Glutamate Biochemistry chemistry.chemical_compound Receptors Kainic Acid Drug Discovery General Pharmacology Toxicology and Pharmaceutics Pharmacology Kainic Acid Natural product Organic Chemistry Rational design Stereoisomerism chemistry Drug Design Thermodynamics Molecular Medicine NMDA receptor Selectivity Protein Binding Ionotropic effect |
| Zdroj: | ChemMedChem. 6:498-504 |
| ISSN: | 1860-7187 1860-7179 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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