Synthesis of 1,4-diphenylbutadiene derivatives: novel inducer of tissue-type plasminogen activator (t-PA) in cultured bovine endothelial cells

(E,E)-1,4-Diphenylbutadiene derivatives were synthesized by utilizing the Stobbe reaction of dimethyl succinate as a key step. Their stereoisomers were also synthesized stereoselectively by means of the cross-coupling reaction of the vinylstannanes and the vinylbromides, which were obtained from the propiolic acid esters by stereoselective hydrostannation, as a key step. To discover novel stimulators of fibrinolysis in vascular endothelial cells, the synthesized compounds were added to cultured bovine endothelial cells to determine the activity of the plasminogen activator in the conditioned medium. Of the synthesized compounds, three compounds were found to stimulate the activity of the plasminogen activator in endothelial cells. In addtition, these compounds inhibited thrombus formation in a rat model of venous thrombosis.