Synthesis and antiulcer activity of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinoli nes and related compounds.
A series of 4-substituted 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolin es 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-N-methylamino)-1-ethyl-8-[(5-fluoro-6-methoxy-2-benzimidazoly l) sulfinylmethyl]-1-ethyl-1,2,3,4-tetrahydroquinoline (XVIIx) were found to have potent activity. The structure-activity relationships are discussed.
Uchida
M
M
Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Japan.
Chihiro
M
M
Morita
S
S
Yamashita
H
H
Yamasaki
K
K
Kanbe
T
T
Yabuuchi
Y
Y
Nakagawa
K
K
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D017506:H(+)-K(+)-Exchanging ATPase; D008297:Male; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013440:Sulfides / Q000138:chemical synthesis / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D011804:Quinolines; D013440:Sulfides; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase