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

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

WR182393, a guanidinoimidazolidinedione derivatives with potent causal prophylactic antimalarial activity by intramuscular injection, was previouly 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 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 yoelii in mouse by oral administration.

Original languageEnglish (US)
Pages (from-to)6472-6481
Number of pages10
JournalJournal of Medicinal Chemistry
Volume48
Issue number20
DOIs
StatePublished - Oct 6 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Zhang, Q., Guan, J., Sacci, J., Ager, A., Ellis, W., Milhous, W., Kyle, D., & Lin, A. J. (2005). Unambiguous synthesis and prophylactic antimalarial activities of imidazolidinedione derivatives. Journal of Medicinal Chemistry, 48(20), 6472-6481. https://doi.org/10.1021/jm0504252