Sulfamoyl Group Research Articles

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.

Antimalarial Properties of a Variety of Substituted p-Sulfamoylphenylazo Compounds

A wide variety of substituted p-sulfamoylphenylazo compounds were prepared, and their activity against Plasmodium berghei in mice was studied. A study of the effects of substitution in the sulfamoyl group revealed that substitution by pyrimidine, methylpyrimidine, and hexylresorcinol greatly increased the antimalarial activity, while substitution by thiazole, methylthiazole, and 2-methyl-3,4-thiadiazole did not lead to a comparable increase in activity. The least activity was seen in compounds with 2-pyridyl as the substituent. Coupling compounds derived from sulfa drugs, hexylresorcinol, and 1,3-dimethyl-6-aminouracil were either active or curative at lower doses than the remainder of the compounds evaluated. With pyrimidine as the substituent, an amino group in position 4 or 5 was necessary for antimalarial activity. It was also found that coplanarity is not an essential structural requirement for antimalarial activity.

Biological activities of drugs. VII. Structure-activity relationship of sulfonamide carbonic anhydrase inhibitors.

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, pKa, 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.

Biological activities of drugs. VI. Structure-activity relationship of sulfonamide carbonic anhydrase inhibitors. (1).

A study was made of correlation of carbonic anhydrase inhibitory activity with the chemical structures of 19 derivatives of benzenesulfonamide and 3 heterocyclic sulfonamides in reference to the physicochemical properties of the compounds. A linear correlation was observed for Hammett's σ factor against pKa, chemical shift of the sulfamoyl protons, and valence-force constant of the S=O bond. Inhibitory activity increased with a decrease of pKa, and with an increase of Hammett's σ factor, chemical shift of the sulfamoyl protons, and the S=O valence-force constant of the sulfamoyl group. A close correlation was also found between the inhibitory activity and water solubility of the unionized molecules of benzenesulfonamides except for p-CH3NH and o-NO2 derivatives.

Pharmaceutical studies on phenothiazine derivatives. V. Photodegradation of thioproperazine, acetylpromazine, and its sulfoxide

Photodecomposition of thioproperazine (III), acetylpromazine (V), and its sulfoxide (VI) was carried out by irradiation of fluorescent light on their acid solution and in the lighting cabinet described in the preceding paper. III rapidly underwent photooxidation in air, in the presence of maleic acid, to its sulfoxide (IV). This maleic acid is known to prevent photohydrolysis of the sulfamoyl group in the 2-position of phenothiazine ring. Stability of V and VI to light was compared with that of propericiazine and its sulfoxide, and that of III and IV, and it was found that V and VI are more stable than the other compounds.

Alkylsulfonyltoluene Derivatives (Diuretics. II.)

The alkyl groups with a tertiary amino group at the β-carbon atom or an imino group at the α-carbon atom were introduced into the sulfamoyl or N-substituted sulfamoyl group of 4-methylsulfonyl-o-toluenesulfonamides to investigate possible alteration of the biological activity of the parent sulfonamides.