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

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.