Synthesis and biological activity of glutamic acid derivatives

In order to develop new specific glutamate analogues at metabotropic glutamate receptors, Diels-Alder, 1–4 ionic and radical reactions were performed starting from (2S)-4-methyleneglutamic acid.Preliminary pharmacological evaluation by measuring IP accumulation using rat forebrain synaptoneurosomes has shown that (2S)-4-(2-phthalimidoethyl)glutamic acid (3a), (2S)-4-(4-phthalimidobutyl)glutamic acid (3b) and 1-[(S)-2-amino-2-carboxyethyl]-3,4-dimethylcyclohex-3-ene-1-carboxylic acid (8) presented moderate antagonist activities.