Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents

Bioorg Med Chem Lett. 2009 Feb 1;19(3):624-6. doi: 10.1016/j.bmcl.2008.12.058. Epub 2008 Dec 24.

Abstract

Within the frame of the design of prodrug candidates to deliver a C-alkylamidine antimalarial agent, we showed that specific O-substitutions were needed on the alkylamidoxime structure. Among the newly synthesized molecules, bis-oxadiazolone and bis-O-methylsulfonylamidoxime derivatives induced a complete clearance of parasitemia in mice after oral administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antimalarials / pharmacology*
  • Antioxidants / pharmacology*
  • Chemistry, Pharmaceutical / methods
  • Dose-Response Relationship, Drug
  • Drug Design
  • Humans
  • Malaria / drug therapy*
  • Mice
  • Models, Chemical
  • Parasitemia / drug therapy*
  • Plasmodium falciparum
  • Prodrugs

Substances

  • Antimalarials
  • Antioxidants
  • Prodrugs