Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid

M J Valli; D D Schoepp; R A Wright; B G Johnson; A E Kingston; R Tomlinson; J A Monn

doi:10.1016/s0960-894x(98)00352-7

Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid

Bioorg Med Chem Lett. 1998 Aug 4;8(15):1985-90. doi: 10.1016/s0960-894x(98)00352-7.

Authors

M J Valli¹, D D Schoepp, R A Wright, B G Johnson, A E Kingston, R Tomlinson, J A Monn

Affiliation

¹ Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

PMID: 9873471
DOI: 10.1016/s0960-894x(98)00352-7

Abstract

A series of N1-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been prepared as constrained analogs of gamma-substituted glutamic acids and examined for their effects at recombinant metabotropic glutamate receptor (mGluR) subtypes in vitro. Appropriate substitution of the N1 position of 2R,4R-APDC resulted in the identification of a number of selective group II mGluR antagonists.

MeSH terms

Humans
Hydrolysis
Phosphatidylinositol Phosphates / metabolism
Proline / analogs & derivatives*
Proline / chemical synthesis
Proline / chemistry
Proline / pharmacology
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Recombinant Proteins / antagonists & inhibitors
Stereoisomerism
Structure-Activity Relationship

Substances

4-aminopyrrolidine-2,4-dicarboxylic acid
Phosphatidylinositol Phosphates
Receptors, Metabotropic Glutamate
Recombinant Proteins
Proline