Synthesis, biological evaluation and structure-activity relationships of new phthalazinedione derivatives with vasorelaxant activity

Eur J Med Chem. 2014 Jul 23:82:407-17. doi: 10.1016/j.ejmech.2014.05.052. Epub 2014 May 24.

Abstract

Five series of 1,4-phthalazinedione derivatives were synthesized in good yields. Vasorelaxant activity of these new derivatives was measured on either intact or endothelium-denuded isolated rat thoracic aortic rings pre-contracted with phenylephrine. Most of studied compounds, substituted in both nitrogen atoms, attained practically the total relaxation of the organ at low micromolar concentrations. The presence of functional endothelium significantly reduced the EC50 values for most of studied compounds. Some structure-activity relationships were established and compounds 2d and 5d can be considered as new leads for further modifications.

Keywords: Endothelium; Phthalazinedione derivatives; Rat aortic rings; SAR; Synthesis; Vasorelaxant activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / cytology
  • Aorta, Thoracic / drug effects*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Male
  • Molecular Structure
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects*
  • Phthalazines / chemical synthesis
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Rats
  • Rats, Inbred WKY
  • Rats, Wistar
  • Structure-Activity Relationship
  • Vasodilator Agents / chemical synthesis
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology*

Substances

  • Phthalazines
  • Vasodilator Agents