Unambiguous Synthesis and Prophylactic Antimalarial Activities of Imidazolidinedione Derivatives

摘要

WR 182393, a guanidinoimidazolidiondione derivative with potent causal prophylactic antimalarial activity by intramuscular injection, was previously prepared by treatment of chloro-proguanil 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 unamgibuous 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 yoelil in mouse by oral administration.