Synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin

J Med Chem. 1998 Oct 8;41(21):4101-8. doi: 10.1021/jm9810147.

Abstract

Fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (BF3,Et2O or TMSCl catalysis or Mitsunobu reaction). Ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. Ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the Mitsunobu reaction. Although in vitro antimalarial activities of ethers toward Plasmodium falciparum W-2 asiatic strain are moderate, in vivo activities against Plasmodium berghei (NT 173) are excellent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Artemisinins*
  • Drug Evaluation, Preclinical
  • Female
  • Inhibitory Concentration 50
  • Malaria / drug therapy
  • Mice
  • Plasmodium berghei
  • Plasmodium falciparum / drug effects
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Artemisinins
  • Sesquiterpenes
  • artenimol