4-substituted 5-[m-(trifluoromethyl)phenoxy]primaquine analogues as potential antimalarial agents

J Med Chem. 1985 Nov;28(11):1564-7. doi: 10.1021/jm00149a004.

Abstract

Five 4-substituted 5-[m-(trifluoromethyl)phenoxy]primaquine analogues were synthesized and tested for radical curative activity against Plasmodium cynomolgi in Rhesus monkeys and for blood schizonticidal antimalarial activity against Plasmodium berghei in mice. In addition, they were evaluated for causal prophylactic antimalarial activity against Plasmodium berghei yoelii in mice. One compound, 4-ethyl-5-[m-(trifluoromethyl)phenoxy]primaquine (2b), showed radical curative activity equivalent to 4-methyl-5-[m-(trifluoromethyl)phenoxy]primaquine (2a). A second compound showed radical curative activity slightly less than 2a and 2b; the remaining three compounds were not active against P. cynomolgi. All five compounds showed much higher blood schizonticidal activity and less toxicity than primaquine; however, none of the compounds were as active as 2a. Three of four compounds tested showed high activity against P. berghei yoelii.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Chemical Phenomena
  • Chemistry
  • Macaca mulatta
  • Malaria / drug therapy*
  • Mice
  • Plasmodium
  • Primaquine / analogs & derivatives*
  • Primaquine / chemical synthesis
  • Primaquine / therapeutic use
  • Structure-Activity Relationship

Substances

  • Primaquine