New imidazolidinedione derivatives as antimalarial agents

Abstract

A series of new N-alky- and N-alkoxy-imidazolidinediones was prepared and assessed for prophylactic and radical curative activities in mouse and Rhesus monkey models. New compounds are generally metabolically stable, weakly active in vitro against Plasmodium falciparum clones (D6 and W2) and in mice infected with Plasmodium berghei sporozoites. Representative compounds 8e and 9c showed good causal prophylactic activity in Rhesus monkeys dosed 30mg/kg/day for 3 consecutive days by IM, delayed patency for 19–21days and 54–86days, respectively, as compared to the untreated control. By oral, 9c showed only marginal activity in causal prophylactic and radical curative tests at 50mg/kg/day×3 and 30mg/kg/day×7 plus chloroquine 10mg/kg for 7days, respectively.