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

A series of 1N-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been prepared as constrained analogs of γ-substituted glutamic acids and examined for their effects at recombinant metabotropic glutamate receptor (mGluR) subtypes in vitro. Appropriate substitution of the 1N position of 2R,4R-APDC resulted in the identification of a number of selective group II mGluR antagonists.