STRUCTURE-ACTIVITY-RELATIONSHIPS IN A SERIES OF 3-SULFONYLAMINO-2-(1H)-QUINOLONES, AS NEW AMPA KAINATE AND GLYCINE ANTAGONISTS

This paper describes the design and synthesis of a new class of molecules, the 3-sulfonylamino-2-(1H)-quinolones, which are potent and selective antagonists at both the AMPA/kainate site as well as at the NMDA-associated glycine site. The molecules were characterized by their binding affinities to rat cortical membranes and by electrophysiology on Xenopus oocytes injected with mRNA isolated from rat cerebral cortex. The most potent compound 61 has an IC50 of 0.09 mu M for binding at the AMPA/kainate site, and 0.16 mu M in oocyte electrophysiology.