2,3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as Potent and Selective Antagonists of Metabotropic Glutamate Receptors

Bioorg Med Chem Lett. 1998 Oct 20;8(20):2849-54. doi: 10.1016/s0960-894x(98)00510-1.

Abstract

2-(9-Xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3' disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3' substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100 microns).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Excitatory Amino Acid Antagonists / chemical synthesis*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glycine / analogs & derivatives*
  • Glycine / chemistry
  • Glycine / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Neurons / drug effects
  • Prosencephalon / drug effects
  • Rats
  • Receptors, Glutamate / drug effects*
  • Structure-Activity Relationship

Substances

  • Cyclopropanes
  • Excitatory Amino Acid Antagonists
  • Receptors, Glutamate
  • Glycine