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

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.