(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.
D000085:Acetates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000138:chemical synthesis*; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D009318:Natriuresis / Q000187:drug effects; D010642:Phenoxyacetates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology
D000085:Acetates; D002712:Chlorides; D004232:Diuretics; D010642:Phenoxyacetates; D014753:Vinyl Compounds; D012964:Sodium; D011188:Potassium