Orally active amino functionalized antimalarial 1,2,4-trioxanes

Using readily available trioxanes 6a–b, a new series of amino functionalized 1,2,4-trioxanes 8a–e and 9a–e have been prepared and evaluated for antimalarial activity against multi-drug resistant Plasmodium yoelii in Swiss mice model. Several of these novel trioxanes are orally more active than the parent trioxanes 6a–b. Antimalarial activity of amino functionalized trioxane 9a, the most potent compound in the series, is very close to that of β-arteether.