Competitive NMDA receptor antagonists: synthesis of β-ketophosphonate-substituted piperidine carboxylic acid derivatives

Abstract A series of substituted 3(S)-phosphonoacetyl-2(R)-piperidinecarboxylic acids has been synthesized. Substitution with a methyl group in the 4 position, trans to the phosphonoacetyl group has been found to substantially increase binding affinity (IC 50 =15 nM vs [ 3 H] CPP) at the NMDA receptor complex over that of the parent compound (IC 50 =40 nM).