Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives.

Quan Zhang, Jian Guan, John Sacci, Arba Ager, William Ellis, Wilbur Milhous, Dennis Kyle, Ai J Lin

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.

Journal of medicinal chemistry 2005 Oct 6

filter terms:

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.

Citation

Quan Zhang, Jian Guan, John Sacci, Arba Ager, William Ellis, Wilbur Milhous, Dennis Kyle, Ai J Lin. Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives. Journal of medicinal chemistry. 2005 Oct 6;48(20):6472-81