5-Sulfamoylorthanilic acids, a sulfonamide series with salidiuretic activity

Abstract

A series of 4,N-disubstituted 5-sulfamoylorthanilic acids was synthesized by nucleophilic substitution reactions starting either from 2,4-dihalogeno-5-sulfamoylbenzenesulfonic acids or, in most cases, from phenyl 2,4-dihalogeno-5-sulfamoylbenzenesulfonates. The latter method is based on the relative stability of the phenoxysulfonyl group to nucleophiles, e.g., amines, phenols, and thiols, and the possibility of smooth hydrolytic or hydrogenolytic cleavage as a final step, with formation of the SO3H group. On evaluation of these compounds for salidiuretic activity in rats orally (po), and in dogs orally and intravenously (iv), a number of highly active substances was found; the best had a threshold dose of 0.02 mg/kg po in dogs. The results are given in tables, and the structure-activity relationships within the series are discussed. Besides the known effect of the phenoxy radical, an outstanding activating effect was shown by the butylsulfonyl and cycloalkylsulfonyl radicals and by the N-methylanilino radical in particular when they were located in the 4-position of the orthanilic acid molecule. The sulfanilic acid isomers corresponding to three of the most active compounds were synthesized and proved to be completely inactive in rats.

Kinetic Dissection of the Catalytic Mechanism of Taurine:α-Ketoglutarate Dioxygenase (TauD) from Escherichia coli

“…MS: m/z ) 204 (MH + ). 1,1-[ 2 H] 2 -2-aminoethane-1-sulfonic acid phenyl ester was converted to the free acid via hydrogenolysis of the phenolic carbon-oxygen bond (Scheme 2, step E) in a procedure similar to that described by Sturm et al(19). The ester (0.30 g…”

Synthesis and biological activity of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine: water-soluble and peripherally selective adenosine agonists.

“…30 Thus, the proportion of the analog that exists in charged form at physiological pH would be much greater for a sulfonic acid than for a carboxylic acid. Also, the π-value of a sulfonate group (−4.76) suggests a somewhat greater tendency to partition into an aqueous phase than the value for a carboxylate (−4.36).…”

Sulfonamide as an Activating Group for the Synthesis of Poly(aryl ether sulfonamide)s by Nucleophilic Aromatic Substitution

“…The sulfonamide moiety has also been shown to be a stable group that can stand up to an array of reaction conditions and has led to the extensive use of sulfonamides as protecting groups for amines − and sulfonic acids during multistep syntheses. Sulfonamides have also been shown to activate aryl halides at the para position for nucleophilic displacement reactions under very mild conditions. − The mild reaction conditions suggest that the sulfonamide is strongly activated. Surprisingly, to the best of our knowledge, sulfonamides have never been used to activate for S N Ar polymerization.…”