Structure-activity relationship of anti-malarial spongean peroxides having a 3-methoxy-1,2-dioxane structure

In order to study the structure-activity relationship of anti-malarial spongean peroxides, several analogues concerning with the 6-methoxyacetyl moiety and the 3-pentyl residue in methyl 2-(3-methoxy-3-pentyl-1,2-dioxan-6-yl) acetate were synthesized and evaluated for anti-malarial activity. The tert-butyl ester analogue 14 showed stability in mouse serum and a high selectivity index against the malaria parasite, Plasmodium falciparum, and the citronellyl analogue 31 exhibited the strongest in vitro antimalarial activity among them, and the imidazole analogue 25 showed desirable in vivo anti-malarial activity against P. berghei infected mice. (C) 2004 Elsevier Ltd. All rights reserved.