Synthesis and anticoagulant activities of substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins

Arch Pharm (Weinheim). 2006 Jun;339(6):319-26. doi: 10.1002/ardp.200500149.

Abstract

Different substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins are the final products when 4-hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o-, m,- or p-position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time. The X-ray crystal structure analysis of 3-[6-oxo-(6H, 7H)-benzopyrano[4,3-b]benzopyran-7-yl]-4-hydroxy-2H-1-benzopyran-2-one 1 confirmed the structure of this compound. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effect of the derivatives with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compounds are 3-(3'-hydroxybenzylidene)-2,4-diketochroman 4 and 3,3'-(2-pyridylmethylene)-bis-4-hydroxy-2H-1-benzopyran-2-one 11 with low toxicity and dose-dependent anticoagulant activity in vivo.

Publication types

  • Comparative Study

MeSH terms

  • 4-Hydroxycoumarins / chemical synthesis
  • 4-Hydroxycoumarins / toxicity*
  • Animals
  • Anticoagulants / chemical synthesis
  • Anticoagulants / toxicity*
  • Blood Coagulation / drug effects*
  • Chromans / chemical synthesis
  • Chromans / toxicity*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Lethal Dose 50
  • Male
  • Mice
  • Molecular Structure
  • Warfarin / toxicity
  • Whole Blood Coagulation Time

Substances

  • 4-Hydroxycoumarins
  • Anticoagulants
  • Chromans
  • Warfarin