Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds

Abstract

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.

Properties and Diversity of (Na-K-C1) Cotransporters

“…BSTBA is a bumetanide analog, which is a potent loop diuretic (66), and contains a photoreactive benzophenone group. We have used [3Hj4-benzoyl-5-sulfamoyl-3-(3thenyloxy) benzoic acid ([3HjBSTBA) to photo label membranes from dog kidney, duck red cells, and shark rectal gland (24, 39-4 1).…”

2,4‐diamino‐6‐pteridinecarboxaldehyde and an Azobenzene Derivative Are Produced by Uv Photodegradation of Methotrexate

“…This result suggests that I1 has an E configuration with regard to the N=N double bond. Using the method of Nielsen et al (1975), this compound was easily obtained in nearly quantitative yield by reduction of N -b -nitrobenzoy1)-L-glutamic acid.…”

Purification of proteins of the Na/Cl cotransporter from membranes of Ehrlich ascites cells using a bumetanide-sepharose affinity column

“…This analogue of bumetanide, described by Nielsen et al (1975), has potent diuretic activity. Haas and Forbush (1987) showed that BSTBA competes with [3H]-bumetanide in reversible binding and that BSTBA itself binds reversibly with high affinity to the membranes.…”