Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds.
Various 4-substituted 3-alkylamino-, 3-alkoxy-, 3-alkylthio-, and 3-alkyl-5-sulfamoylbenzoic acids related to known aminobenzoic acid diuretics were synthesized and screened for their diuretic properties in dogs. The tabulated results from a 3-hr test period revealed that generally the diuretic profile and potency could be retained when 3-alkoxy, 3-alkylthio, and 3-phenethyl were substituted for the 3-alkylamino moiety. The high potency of several 3-alkoxy-, 3-alkylthio-, and 3-phenethyl-4-benzoyl-5-sulfamoylbenzoic acids confirmed previous suggestions that the apparent diuretic effect of 4- and 5-alkylamino-6-carboxy-3-phenyl-1,2-benzisothiazole 1,1-dioxides originates from the corresponding 4-benzoyl-5-sulfamoylbenzoic acid derivatives due to an existing equilibrium in plasma. 4-Benzoyl-5-sulfamoyl-3-(3-thenyloxy) benzoic acid (118) is among the most potent benzoic acid diuretics hitherto synthesized and shows significant diuretic activity in dogs at 1 mug/kg. The results obtained with different 3-substituted 4-phenyl-5-sulfamoylbenzoic acids supported the earlier concept regarding the steric influence of the 4-substituent on the diuretic potency of sulfamoylbenzoic acid diuretics.
D062365:Aminobenzoates / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D002712:Chlorides / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013329:Structure-Activity Relationship; D013449:Sulfonamides
D062365:Aminobenzoates; D002712:Chlorides; D004232:Diuretics; D013449:Sulfonamides; D012964:Sodium; D011188:Potassium