Synthesis and pharmacological characterization at glutamate receptors of the four enantiopure isomers of tricholomic acid

J Med Chem. 2008 Apr 10;51(7):2311-5. doi: 10.1021/jm701394a. Epub 2008 Mar 14.

Abstract

The two enantiomeric pairs of erythro- and threo-amino-(3'-hydroxy-4',5'-dihydro-isoxazol-5'-yl)-acetic acids were synthesized via the 1,3-dipolar cycloaddition of bromonitrile oxide to ( R)- or ( S)-3-( tert-butoxycarbonyl)-2,2-dimethyl-4-vinyloxazolidine. The pharmacological profiles of the studied amino acids reflect the relationship between the activity/selectivity and the stereochemistry of the two stereogenic centers: while the (2 S,5' S) stereoisomer is an agonist at the AMPA and KA receptors, its (2 R,5' R) enantiomer interacts selectively with the NMDA receptors; the (2 S,5' R) stereoisomer is the only one capable to activate the mGluRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Animals
  • CHO Cells
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • Cyclization
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / chemistry
  • Glycine / pharmacology
  • Humans
  • Isoxazoles / chemical synthesis*
  • Isoxazoles / chemistry
  • Isoxazoles / pharmacology*
  • Molecular Structure
  • Rats
  • Receptors, Glutamate / drug effects*
  • Receptors, Glutamate / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Isoxazoles
  • Receptors, Glutamate
  • tricholomic acid
  • Glycine