Synthesis of conformationally-constrained stereospecific analogs of glutamic acid as antagonists of metabotropic receptors

Rigid analogs of ACPD have been synthesized to mimick different potential conformations of ACPD in aqueous solution. One of them, (±)-ABHD-I is a competitive antagonist at mGluR1a receptor with a K B value of 300 μM. Several norbornane-derived rigid analogs of glutamic acid and ACPD have been prepared by the hydantoin route. One of them, (±)-ABHD I, tested on a mGluR1a receptor, had no agonist activity at 1 mM concentration, but displayed a significant antagonist activity (K B = 300 μM).