(3SR,4aRS,6SR,8aRS)-6-(1H-Tetrazol-5-yl)decahydroisoquinoline-3-carboxylic Acid, a Novel, Competitive, Systemically Active NMDA and AMPA Receptor Antagonist
| Autor: | Paul L. Ornstein, David Lodge, Macklin Brian Arnold, Darryle Darwin Schoepp, Joseph P. Tizzano, N. K. Allen, J. D. Leander |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Stereochemistry
medicine.drug_class Carboxylic acid Tetrazoles AMPA receptor Binding Competitive Receptors N-Methyl-D-Aspartate Mice Receptors Kainic Acid Drug Discovery medicine Animals Receptors AMPA Columbidae Receptor chemistry.chemical_classification Molecular Structure Antagonist Glutamate receptor Isoquinolines Receptor antagonist Amino acid nervous system chemistry Molecular Medicine NMDA receptor Excitatory Amino Acid Antagonists |
| Zdroj: | Journal of Medicinal Chemistry. 38:4885-4890 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | We report the synthesis and characterization of 6 (LY246492), which is a competitive N-methyl-D-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propanoic acid (AMPA) receptor antagonist. Tetrazole-substituted amino acid 6 was prepared in four steps from the recently described aldehyde 7. The optical isomers (-)-6 and (+)-6 were obtained from the same sequence of reactions using the corresponding isomers of 7. The compound displaces both NMDA and AMPA receptor binding and antagonizes depolarizations in cortical slices evoked by both NMDA and AMPA. In mice and pigeons, the compound showed antagonism of responses mediated through NMDA and AMPA receptors. Using the resolved optical isomers of 6, both NMDA and AMPA antagonist activities were found to reside in a single isomer, (-)-6. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|