Studies on Proton Pump Inhibitors. II. : Synthesis and Antiulcer Activity of 8-[(2-Benzimidazolyl)-sulfinylmethyl]-1, 2, 3, 4-tetrahydroquinolines and Related Compounds

Abstract

Many 8-[(2-benzimidazolyl)sulfinylmethyl]-1, 2, 3, 4-tetrahydroquinoline derivatives were synthesized and tested for their (H⁺ + K⁺)adenosine triphosphatase (ATPase)-inhibitory and antisecretory activities against histamine-induced gastric acid secretion in rats. These sulfinyl compounds were synthesized by the oxidation of the corresponding sulfides, which were obtained from the reaction of 8-chloromethyl-1, 2, 3, 4-tetrahydroquinolines and 2-mercaptobenzimidazoles in the presence of potassium carbonate. All compounds tested were potent inhibitors of (H⁺ + K⁺)ATPase. Most of the compounds showed antisecretory activity. Among them, 8-[(2-benzimidazolyl)sulfinylmethyl]-1-ethyl-1, 2, 3, 4-tetrahydroquinoline (IXa) was found to have the most potent activity. The structure-activity relationships are discussed.