Synthesis and preliminary biological evaluation of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives as group I selective metabotropic glutamate receptor ligands

ChemMedChem. 2006 Mar;1(3):358-65. doi: 10.1002/cmdc.200500071.

Abstract

The first series of 2'-substituted 2-(3'-carboxybicyclo[1.1.1]pentyl)glycine derivatives, (2R)- and (2S)-(2',2'-dichloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (10) and (11), and 2-(2'-chloro-3'-carboxybicyclo[1.1.1]pentyl)glycine (12) were synthesized and evaluated as mGluR ligands. Compounds 11 and 12 were shown to be competitive group I mGluR antagonists. These results are also discussed in light of docking studies with both the active (closed) and inactive (open) conformations of mGluR1.

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / metabolism
  • Bridged Bicyclo Compounds / pharmacology*
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / metabolism
  • Glycine / pharmacology
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Receptors, Metabotropic Glutamate / drug effects*
  • Receptors, Metabotropic Glutamate / metabolism
  • Structure-Activity Relationship

Substances

  • Bridged Bicyclo Compounds
  • Ligands
  • Receptors, Metabotropic Glutamate
  • UPF 596
  • Glycine