Aminobenzioc acid diuretics. 8.(2) 3, 4-Disubstituted 5-methylsulfonylbenzioc acids and related compounds

Various 2, 4- and 3, 4-disubstituted 5-methylsulfonylbenzoic acids were synthesized as methylsulfonyl analogues of previously described 5-sulfamoylbenzoic acid diuretics. The results of the diuretic screening in dogs reveal that substitution of the sulfamoyl group by the spatially and sterically similar methylsulfonyl group does not affect the diuretic pattern but leads generally to somewhat decreased potency. For the highly potent 3-benzylamino-4-phenoxy-5-methylsulfonylbenzoic acid the corresponding 5-methylthio and 5-methylsulfinyl analogs were prepared and found still to exhibit diuretic activity. Internal aldol condensation and subsequent dehydration of 3-benzylamino-and 3-n-butylamino-4-benzoyl-5-methylsulfonylbenzoic acid provided the corresponding inactive 4-alkylamino-6-carboxy-2, 3-dihydro-3-hydroxy-3-phenylbenzo[b]thiophene 1, 1-dioxides and 4-alkylamino-6-carboxy-3-phenyl-benzo[b]thiophene 1,1-dioxides.