A rational approach to the design of selective substrates and potent nontransportable inhibitors of the excitatory amino acid transporter EAAC1 (EAAT3). New glutamate and aspartate analogues as potential neuroprotective agents

Two three-dimensional receptor interaction models for EAAT substrates and n ontransportable inhibitors have been developed, and new glutamate (Glu) and aspartate (Asp) analogues have been synthesized. The analogues la and 3 re present novel lead compounds for the development of EAAT substrates and non transportable inhibitors, selective for EAATs over iGluRs, as possible neur oprotective agents useful to minimize the progression of chronic or acute n eurodegenerative diseases, The role played by the protonatable amine functi on in the interaction with EAATs has been discussed.