2,3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors

I Collado; J Ezquerra; A Mazón; C Pedregal; B Yruretagoyena; A E Kingston; R Tomlinson; R A Wright; B G Johnson; D D Schoepp

doi:10.1016/s0960-894x(98)00510-1

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.

Authors

I Collado¹, J Ezquerra, A Mazón, C Pedregal, B Yruretagoyena, A E Kingston, R Tomlinson, R A Wright, B G Johnson, D D Schoepp

Affiliation

¹ Centro de Investigación Lilly, SA, Madrid, Spain.

PMID: 9873635
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