Synthesis and structure-activity relationships of N-substituted 2- 2-imidazolylsulfinyl methyl anilines as a new class of gastric H /K -ATPase inhibitors

Abstract:  Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulf inyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors. Yamakaw a T, Matsukura H, Nomura Y, Yoshioka M, Masaki M, Igata H, Okabe S. Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama, Japan. A series of N-substituted 2-[(2-imidazolylsulf inyl)methyl]anilines (3) was synthesized and evaluated for its biological activity against gastric H+/K(+)-ATPase prepared from rabbit stomach and gastric acid secretions in Heidenhain pouch dogs. Monoalkyl substituents on the nitrogen atom of the aniline moiety markedly inhibited the enzyme activity to the same degree as omeprazole, a representative H+/K(+)-ATPase inhibitor. Most of these compounds, administered at 3 mg/kg i.v. inhibited histamine-stimulated gastric acid secretion. The inhibitory activity of these derivatives on the enzymes at pH 6.0 was more potent than that at pH 7.4, and was distinctly correlated to stability in aqueous solution at pH 5.0. PMID: 1663837 [PubMed - indexed for MEDLINE]