Substituted 2-anilines as Potential Inhibitors of H+/K+ ATPase

Article abstract of DOI:10.1021/jm00401a024

A series of substituted 2-<(2-benzimidazolylsulfinyl)methyl>anilines were synthesized as potential inhibitors of the acid secretory enzyme H⁺/K⁺ ATPase.Substitutions on the aniline nitrogen atom resulted in potent enzyme inhibition in vitro but weak activity in gastric fistula dogs.Electron-donating substituents on the aniline ring enhanced in vitro and in vivo potency relative to the unubstituted analogue.The potency showed a correlation to the calculated pK_a of the aniline nitrogen atom.Substitutions on the aniline and benzimidazole rings did not further enhance potency.Di- and trisubstituted aniline derivatives were potent inhibitors of the enzyme system.The preferred combination of substituents were a methoxy group on the benzimidazole ring and a single alkyl group on the aniline ring.One such compound, 76, was an effective inhibitor of acid secretion in the dog and was selected for further pharmacological study.