Pyrrolylquinoxalinediones: The importance of pyrrolic substitution on AMPA receptor binding

Pyrrolylquinoxalinediones were synthesized to elucidate the value of pyrrolic substitution pattern on AMPA receptor binding. We discovered that amide and urea residues at the 3′-position at pyrrol ring favor affinity to AMPA receptor. Particularly, the phenylurea 13n exhibited a Ki value of 4 nM in AMPA receptor binding and represents the most potent competitive AMPA antagonist reported to date.