Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives

Eur J Med Chem. 2006 Jul;41(7):882-90. doi: 10.1016/j.ejmech.2006.03.007. Epub 2006 May 2.

Abstract

Twenty 4-hydroxycoumarin derivatives were synthesized. Five of them are described for the first time. The X-ray crystal structure analysis of 3,3'-(2,3,4-trimethoxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (7) and 3,3'-(3,5-dimethoxy-4-hydroxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (9) confirmed the structure of these compounds. A comparative pharmacological study of the anticoagulant effect with respect to Warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compound is 3,3'-(4-chlorophenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (12) with low toxicity, very good index of absorption and dose dependent anticoagulant activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Hydroxycoumarins / chemical synthesis
  • 4-Hydroxycoumarins / chemistry*
  • 4-Hydroxycoumarins / pharmacology*
  • 4-Hydroxycoumarins / toxicity
  • Animals
  • Blood Coagulation
  • Crystallography, X-Ray
  • Male
  • Mice
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • 4-Hydroxycoumarins