Orally active 1,2,4-trioxepanes: Synthesis and antimalarial activity of a series of 7-arylvinyl-1,2,4-trioxepanes against multidrug-resistant Plasmodium yoelii in Swiss mice

Abstract

7-Arylvinyl-1,2,4-trioxepanes 7a– d, 8a– d, 9a– d, 10a– d, 11a– c, and 12a– c, prepared by photooxygenation of homoallylic alcohols 5a– d, were evaluated against multi-drug resistant Plasmodium yoelii nigeriensis in Swiss mice by oral and intramuscular routes. Trioxepane 11c, the most active compound of the series, showed more than 98% suppression of parsitaemia at 96 mg/kg by both oral and intramuscular routes. This is the first report on in vivo active 1,2,4-trioxepanes.