Rational Design of a Novel AMPA Receptor Modulatorthrough a Hybridization Approach

摘要

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a family of glutamate ion channels of considerable interest in excitatory neurotransmission and associated disease processes. Here, we demonstrate how exploitation of the available X-ray crystal structure of the receptor ligand binding domain enabled the development of a new class of AMPA receptor positive allosteric modulators (>7) through hybridization of known ligands (>5 and >6), leading to a novel chemotype with promising pharmacological properties.