Studies on proton pump inhibitors. II. Synthesis and antiulcer activity of 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolines and related compounds.
Many 8-[(2-benzimidazolyl)sulfinylmethyl]-1,2,3,4-tetrahydroquinolin e 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-tetrahydro quinoline (IXa) was found to have the most potent activity. The structure-activity relationships are discussed.
Uchida
M
M
Chihiro
M
M
Morita
S
S
Kanbe
T
T
Yamashita
H
H
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; D055598:Chemical Phenomena; D002621:Chemistry; D011522:Protons; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D011522:Protons; D011804:Quinolines; C062128:8-((2-benzimidazolyl)sulfinylmethyl)-1-ethyl-1,2,3,4-tetrahydroquinoline; D000251:Adenosine Triphosphatases