title: 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 30 mg/kg/day for 3 consecutive days by IM, delayed patency for 19-21 days and 54-86 days, respectively, as compared to the untreated control. By oral, 9c showed only marginal activity in causal prophylactic and radical curative tests at 50 mg/kg/day×3 and 30 mg/kg/day×7 plus chloroquine 10 mg/kg for 7 days, respectively.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Ramadas
authors.initials: R
authors.lastname: Sathunuru
authors.forename: ThuLan
authors.initials: T
authors.lastname: Luong
authors.forename: Victor
authors.initials: V
authors.lastname: Melendez
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kozar
authors.forename: Ai J
authors.initials: AJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D048289:Imidazolidines / Q000737:chemistry* / Q000494:pharmacology*; D008253:Macaca mulatta; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei / Q000187:drug effects; D016789:Plasmodium cynomolgi / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D048289:Imidazolidines