Antimalarial sulfide, sulfone, and sulfonamide trioxanes

A series of trioxanes featuring sulfide, sulfone. and sulfonamide snbstitue nts in diverse positions has been prepared. Structure-activity relationship (SAR) generalizations highlight two major factors controlling the antimala rial potency of these new chemical entities: (1) the proximity of the sulfu r-containing substituent to the crucial peroxide bond and (2) the oxidation stale of the sulfur-containing substituent. Generally, sulfones are more a ntimalarially potent than the corresponding sulfides. (C) 2000 Elsevier Sci ence Ltd. All rights reserved.