Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity

Chem Pharm Bull (Tokyo). 2005 Oct;53(10):1324-6. doi: 10.1248/cpb.53.1324.

Abstract

Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design
  • Drug Evaluation, Preclinical
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / enzymology
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Benzamides
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase