Design, Synthesis and Biological Evaluation of Novel bicyclo[1.1.1]pentane-based Omega-Acidic Amino Acids as Glutamate Receptors Ligands

Bioorg Med Chem. 2009 Jan 1;17(1):242-50. doi: 10.1016/j.bmc.2008.11.015. Epub 2008 Nov 14.

Abstract

A novel series of bicyclo[1.1.1]pentane-based omega-acidic amino acids, including (2S)- and (2R)-3-(3'-carboxybicyclo[1.1.1]pentyl)alanines (8 and 9), (2S)- and (2R)-2-(3'-carboxymethylbicyclo[1.1.1]pentyl)glycines (10 and 11), and (2S)- and (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycines (12 and 13), were synthesized and evaluated as glutamate receptor ligands. Among them, (2R)-3-(3'-phosphonomethylbicyclo[1.1.1]pentyl)glycine (13) showed relatively high affinity and selectivity at the NMDA receptor. The results are also discussed in light of pharmacophoric modelling studies of NMDA agonists and antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine
  • Amino Acids, Acidic / chemical synthesis*
  • Amino Acids, Acidic / pharmacokinetics*
  • Bridged Bicyclo Compounds / chemical synthesis
  • Glycine
  • Humans
  • Ligands
  • Pentanes / chemical synthesis
  • Protein Binding
  • Receptors, Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / agonists
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Amino Acids, Acidic
  • Bridged Bicyclo Compounds
  • Ligands
  • Pentanes
  • Receptors, Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Alanine
  • Glycine