Biological Activities of Four Stereoisomers of 2-(4-Methoxy-6, 7, 8, 9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylsulfinyl)-1H-benzimidazole Sodium Salt and Acid-Induced Transformations : Novel Proton Pump Inhibitor

Abstract

The sodium salts (5) of four stereoisomeric benzimidazolylsulfoxides, (Ss, 9R)-(-)-4, (Rs, 9S)-(+)-4, (Ss, 9S)-(-)-4 and (Rs, 9R)-(+)-4, were prepared from optically pure sulfides, (+)-8 and (-)-8. The sulfoxides (4) were transformed into sulfenamides (6) and symmetric disulfides (9) under acidic conditions, without any change of stererochemical configuration at the α-carbon bearing the sulfinyl group. No significant difference was observed among the four stereoisomers in inhibitory activity towards (H⁺+K⁺)-ATPase in vitro. However, (Ss, 9R)-(-)-5 showed more long-lasting antisecretion activity in vivo than that of another enantiomer, (Rs, 9S)-(+)-5.