3-carboxy-4-phosphonocyclopentane amino acids: new metabotropic glutamate receptor ligands

Amino Acids. 2003 Apr;24(3):303-10. doi: 10.1007/s00726-002-0405-6.

Abstract

Two glutamic acid analogs (1 SR,3 RS,4 RS)- and (1 SR,3 SR,4 SR)-1-amino-4-phosphono cyclopentane-1,3-dicarboxylic acids (APCPD) have been synthesized. Pure E-(diethoxy-phosphoryl)-acrylic acid ethyl ester was obtained from ethyl propiolate, phenol and triethylphosphite. It was used as dienophile in a Diels-Alder reaction. Oxidation and cyclization afforded 3-(ethoxy-carbonyl)-4-(diethoxy-phosphoryl)-cyclopentanone. Bucherer-Bergs reaction and hydrolysis yielded APCPD-III and -IV which are inactive on mGlu1a receptor and antagonists on mGlu2 and mGlu8a receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology
  • Binding Sites / drug effects
  • Cell Line
  • Cyclopentanes / chemical synthesis*
  • Cyclopentanes / chemistry
  • Cyclopentanes / pharmacology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Hydrogen Bonding
  • Ligands
  • Models, Chemical
  • Models, Molecular
  • Molecular Structure
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / metabolism*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Cyclopentanes
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Ligands
  • Receptors, Metabotropic Glutamate