Aromatic amino analogues of artemisinin: synthesis and in vivo antimalarial activity

Nine orally active novel artemisinin derivatives were prepared from artemisinin by four-step synthesis, and the compounds were evaluated in the rodent model using multidrug resistant Plasmodium yoelii nigeriensis. All of the compounds exhibited antimalarial activities with the ED₅₀ ranging from 5.41 mg/kg–12.4 mg/kg. Among them, artemisinin derivative bearing N-(4-hydroxy-3-((4-phenylpiperazin-1-yl)methyl)phenyl) moiety (5f) was found to be the most active compound and was found to be three times more potent than artemisinin (ED₅₀ 16.4 mg/kg).