(3SR,4aRS,6SR,8aRS)-6-(1H-Tetrazol-5-yl)decahydroisoquinoline-3-carboxylic Acid, a Novel, Competitive, Systemically Active NMDA and AMPA Receptor Antagonist

1 December 1995

journal article
Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry

Vol. 38 (25) , 4885-4890
https://doi.org/10.1021/jm00025a005

Abstract

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.

Keywords

This publication has 0 references indexed in Scilit: