Studies on proton pump inhibitors. I. Synthesis of 8-[(2-benzimidazolyl)sulfinyl]-5,6,7,8-tetrahydroquinolines and related compounds.
Many 8-[(2-benzimidazolyl)sulfinyl]-5,6,7,8-tetrahydroquinolines were synthesized and examined for their (H+ + K+) adenosine triphosphatase ATPase-inhibitory and antisecretory activities. These sulfinyl compounds could be considered to be rigid analogues of the 2-[(2-pyridyl)methylsulfinyl]benzimidazole class of antisecretory agents. All the compounds tested were potent inhibitors of (H+ + K+)ATPase. Most of the compounds also inhibited histamine-induced gastric acid secretion in rats. Among them, 8-[(5-fluoro-2-benzimidazolyl)sulfinyl]-3-methyl-5,6,7,8-tetrahydroqu inoline (XIVm) was found to have the most potent activity. The structure-activity relationships are discussed.
Uchida
M
M
Morita
S
S
Chihiro
M
M
Kanbe
T
T
Yamasaki
K
K
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*; D002470:Cell Survival / Q000187:drug effects; 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; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D011804:Quinolines; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase