Synthesis and pharmacological investigations of some 4-hydroxycoumarin derivatives

Arch Pharm (Weinheim). 2003 Apr;336(2):83-94. doi: 10.1002/ardp.200390010.

Abstract

The synthesis of ten coumarin derivatives of 4-hydroxycoumarin and various unsaturated ketones and aldehydes is described. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR, and mass-spectral data. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effects of the derivatives with respect to warfarin, showed that the compounds have anticoagulant activity. Compounds 4-hydroxy-3-[1-phenyl-2-(4'-chlorobenzoyl)ethyl]-2H-1-benzopyran-2-one 2b, 4-hydroxy-3-[1-(4-fluorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one 3a, and 3, 3'-p-bromobenzylidene-bis-(4-hydroxy-2H-1-benzopyran-2-one) 4b showed slight acute toxicity and a greater anticoagulant effect than warfarin.

Publication types

  • Comparative Study

MeSH terms

  • 4-Hydroxycoumarins / chemical synthesis*
  • 4-Hydroxycoumarins / pharmacology
  • 4-Hydroxycoumarins / toxicity
  • Administration, Oral
  • Animals
  • Anticoagulants / chemical synthesis*
  • Anticoagulants / pharmacology
  • Anticoagulants / toxicity
  • Blood Coagulation / drug effects
  • Injections, Intraperitoneal
  • Lethal Dose 50
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Mice
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship
  • Toxicity Tests, Acute

Substances

  • 4-Hydroxycoumarins
  • Anticoagulants