Excitatory amino acid receptor ligands: Asymmetric synthesis, absolute stereochemistry and pharmacology of (R)- and (S)-homoibotenic acid
| Autor: | Ulf Madsen, Bjarke Ebert, P. Krogsgaard-Larsen, Francois Bischoff, T. N. Johansen |
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| Rok vydání: | 1995 |
| Předmět: |
Agonist
N-Methylaspartate Stereochemistry medicine.drug_class Clinical Biochemistry Glutamic Acid Pharmaceutical Science Stereoisomerism In Vitro Techniques Ligands Biochemistry Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Ibotenic Acid alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Molecular Biology Cerebral Cortex chemistry.chemical_classification Chiral auxiliary Kainic Acid Organic Chemistry Enantioselective synthesis Glutamic acid Rats Amino acid Chiral column chromatography Receptors Glutamate chemistry Molecular Medicine Enantiomer |
| Zdroj: | Bioorganic & Medicinal Chemistry. 3:553-558 |
| ISSN: | 0968-0896 |
| Popis: | The (R)- and (S)-forms of 2-amino-3-(3-hydroxyisoxazol-5-yl)propionic acid (homoibotenic acid, HIBO) were synthesized, using (S)-BOC-phenylalanine as a chiral auxiliary and their absolute stereochemistry correlated with that of (R)-Br-HIBO. The enantiomeric excesses for (R)-HIBO (1) (> 99.5%) and (S)-HIBO (2) (99.5%) were determined using chiral HPLC. Whereas compounds 1 and 2 were equipotent inhibitors of the binding of [3H]glutamic acid in the presence of calcium chloride, 2 showed AMPA agonist activity and 1 very weak NMDA agonist activity. |
| Databáze: | OpenAIRE |
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