[Structure-activity relationships in the diuretic xipamide (4-chloro-5-sulfamoyl-2', 6' -salicyloxylidide)]

Abstract

The synthesis of various derivatives of 4-chlorosalicylic acid substituted in position 5 is described. The evaluation of their diuretic potency on the rat showed 4-chloro-5-sulfamoyl-2,6-salicyloxylidide (BE 1293, xipamide, Aquaphor) as the most effective one. The normal urinary volume is increased tenfold by a oral dose of 100 mg/kg body weight. All changes in the molecular structure of xipamide, even acetylation, the introduction of a second sulfamoyl group or the exchange of the sulfonic group for the carbonyl group, lead to a decrease in activity.