Synthesis and Antiulcer Activity of 4-Substituted 8-[(2-Benzimidazolyl)sulfinylmethyl]-1, 2, 3, 4-tetra-hydroquinolines and Related Compounds

Abstract

A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1, 2, 3, 4-tetrahydroquinolines was synthesized and examined for their (H⁺+K⁺)adenosine triphosphatase (ATPase)-inhibitory and antisecretory activities against histamine-induced gastric acid secretion in rats. Many compounds tested were potent inhibitors of (H⁺+K⁺)ATPase. Most compounds showed antisecretory activity. The antiulcer activity against water-immersion stress-induced gastric ulcer, aspirin-induced gastric ulcer and agstric necrosis induced by hydrochloric acid also were tested in the rat. Some of these compounds, in particular, 4-(N-allyl-N-methylamino)-1-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazolyl) sulfinylmethyl]-1ehtyl-1, 2, 3, 4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed.