Biological Activities of Drugs. VII. Structure-Activity Relationship of Sulfonamide Carbonic Anhydrase Inhibitors. (2)

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Diuretic and natriuretic activities and duration of the diuretic action in rats were studied with 22 sulfonamide derivatives. In order to clarify the active form of the sulfonamides, the effect of pH of the rat body fluid on the diuretic activity was studied. 1) The diuretic and natriuretic activities of the sulfonamides increased with an increase of their carbonic anhydrase inhibitory activity except for o-substituted benzenesulfonamides, disubstituted benzenesulfonamides and 2-amino-1,3,4-thiadiazole-5-sulfonamide. 2) A close correlationship of diuretic and natriuretic activities with the electronic characteristics of the sulfamoyl group, such as Hammett's σ factor, pK_a, NMR chemical shift of the sulfamoyl protons and S=O valence-force constant, was observed for the derivatives with some exceptions. 3) A compound having a large partition coefficient and strong albumin binding ability showed long duration of the diuretic action 4) The diuretic and natriuretic activities of sulfonamides were enhanced with an increase of their dissociation constants. The diuretic activity was enhanced under alkalotic conditions. Thus, it was concluded that active form of the sulfonamide carbonic anhydrase inhibitors was the ionized form.
社団法人日本薬学会の論文
1969-10-25