(Vinylaryloxy)acetic acids. A new class of diuretic agents. 1. (Diacylvinylaryloxy)acetic acids

A series of (diacylvinylaryloxy)acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. Several compounds exhibit a high order of activity, the most active being [2,3-dichloro-4-(2,2-diacetylvinyl)-phenoxy]acetic acid (3). This compound is about three times as potent as [2,3-dichloro-4-(2-methylenebutyryl)-phenoxy]acetic acid (ethacrynic acid) but is qualitatively similar in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Saturation of the double bond of 3 virtually abolishes activity lending support to the hypothesis that the saluresis induced by these compounds, like that of ethacrynic acid, is related at least in part to a chemical reaction with protein-bound sulfhydryl groups. Four mercaptan adducts of 3 were prepared; these probably function as prodrugs in producing saluresis. The adduct with mercaptoacetic acid is as active as 3 itself.