title: 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.
abstract: 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.
authors.affiliation: Fukushima Research Laboratories, Toa Eiyo Ltd., Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Aihara
authors.forename: K
authors.initials: K
authors.lastname: Kogi
authors.forename: S
authors.initials: S
authors.lastname: Narita
mesh_terms: 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
chemical_list: D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors