Synthetic study of 2-[(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)-sulfinyl]-1H-benzimidazole analogs and their biological properties as novel proton pump inhibitors.
A series of 2-[(cycloalka[b]pyridinyl)sulfinyl]-1H-benzimidazoles (11) was synthesized and tested for antisecretory activity against pentagastrin-induced gastric acid secretion in rats. A novel benzimidazole derivative containing a cyclohepta[b]pyridine moiety was found to be the most potent among the congeners, which included five- to eight-membered cycloalka[b]pyridine ring systems. Some 2-[(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)sulfinyl]-1H- benzimidazole analogs (14) with various substituents on the aromatic rings showed superior properties to omeprazole (1) in biological examinations in vivo. A diastereoisomer, TY-11345 (28Ba), was selected as a promising agent for further evaluation.
Yamada
S
S
Fukushima Research Laboratories, Toa Eiyo Ltd., Japan.
Goto
T
T
Yamaguchi
T
T
Aihara
K
K
Kogi
K
K
Narita
S
S
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D054328:Proton Pump Inhibitors; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors