Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors.
A series of N-substituted 2-[(2-imidazolylsulfinyl)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.
Yamakawa
T
T
Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama, Japan.
Matsukura
H
H
Nomura
Y
Y
Yoshioka
M
M
Masaki
M
M
Igata
H
H
Okabe
S
S
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D013270:Stomach / Q000201:enzymology*; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D007093:Imidazoles; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase