An absolute structure template for a unique voltage-gated sodium channelbinding site

Abstract

The X-ray crystallographic structures of the mesylate salts of a novel voltage-gated sodium channel-binding ligand R-(−)-BW202W92 and its much less active S-(+)-enantiomer (BW203W92) have been determined to establish their absolute configurations. Each enantiomer exists as two distinct atropisomeric forms in the solid state and the crystal structures for each enantiomer are stabilized by quite distinct patterns of intermolecular hydrogen bonding. Such structural differences will influence the pharmacological properties of the enantiomers and hence dictate their contrasting receptor binding properties.