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.