Synthesis and in vivo antimalarial activity of novel naphthoquine derivatives with linear/cyclic structured pendants.

摘要: Aim: Naphthoquine (NQ) was discovered by our institute as an antimalarial candidate in 1980s, and currently employed artemisinin-based combination therapy partner drug. Resistance to NQ found mouse model laboratory, might emerge future widely used. Methodology: We herein report the design synthesis of derivatives replacing t-butyl moiety with linear/cyclic structured pendants. All target compounds 6a-l intermediates 5a-h were tested for their vivo activity against Plasmodium berghei K173 strain mice. Results: Compounds 6a 6j have a comparable or slightly more potent (the 50% effective dose [ED50], which is required decrease parasitemia 50%: 0.38–0.43 mg/kg) than (ED50: 0.48 mg/kg). Conclusion: The newly designed be promising candidates further research.