title: Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.
abstract: WR182393, a guanidinoimidazolidinedione derivatives with potent causal prophylactic antimalarial activity by intramuscular injection, was previously prepared by treatment of chloroproguanil and diethyl oxalate, yielding a mixture of two closely related isomers. Poor solubility of the mixture made the separation and purification impossible. To overcome the separation problem, new and facile unambiguous syntheses of the two active components were reported. The new synthetic methods facilitate the synthesis of not only the active components, but also their derivatives. To search for compounds with good oral efficacy, a series of carbamate derivatives of the active components were prepared by the new procedure, many of which showed profound causal prophylactic antimalarial activity against Plasmodium yoelii in mouse by oral administration.
authors.affiliation: Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: John
authors.initials: J
authors.lastname: Sacci
authors.forename: Arba
authors.initials: A
authors.lastname: Ager
authors.forename: William
authors.initials: W
authors.lastname: Ellis
authors.forename: Wilbur
authors.initials: W
authors.lastname: Milhous
authors.forename: Dennis
authors.initials: D
authors.lastname: Kyle
authors.forename: Ai J
authors.initials: AJ
authors.lastname: Lin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D010967:Plasmodium yoelii; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D002219:Carbamates; D006146:Guanidines; D007093:Imidazoles; D048289:Imidazolidines; C073156:WR 182393