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

Abstract

A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-l,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 gastric necrosis induced by hydrochloric acid also were tested in the rat. Some of these compounds, in particular, 4-(N-allyl-V-methylamino)-l-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazolyl) sulfinylmethyl]-l-ethyl-l,2,3,4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed. © 1990, The Pharmaceutical Society of Japan. All rights reserved.