Synthesis of new isoxazoline-based acidic amino acids and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

The synthesis of four new isoxazoline-based amino acids being analogues of previously described glutamate receptor ligands is reported and their affinity for ionotropic glutamate receptors is analyzed in comparison with that of selected model compounds. Molecular modelling investigations have been carried out to rationalize the interaction with the NMDA receptors.

New isoxazoline-based acidic amino acids have been synthesized and tested at ionotropic glutamate receptors. Molecular modelling investigations have been carried out to rationalize the interaction with the NMDA receptors.Figure optionsDownload as PowerPoint slideResearch highlights
► Glutamic acid is the main excitatory neurotransmitter in the CNS.
► NMDA receptors are potential therapeutic targets for treatment of CNS disorders.
► New competitive NMDA receptor antagonists have been synthesized and tested.
► The mode of interaction with NMDA/NR2A subunit has been proposed.