2-[[(4-Amino-2-pyridyl) methyl] sulfinyl] benzimidazole H+/K+-ATPase inhibitors. The relationship between pyridine basicity, stability, and activity

…, CA Price, CJ Theobald, AH Underwood

Index: Ife; Dyke; Keeling; Meenan; Meeson; Parsons; Price; Theobald; Underwood Journal of Medicinal Chemistry, 1989 , vol. 32, # 8 p. 1970 - 1977

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Citation Number: 46

Abstract

The benzimidazole sulfoxide class of antisecretory Ht/Kt-ATPase inhibitors need to possess high stability under neutral physiological conditions yet rearrange rapidly at low pH to the active sulfenamide 2. Since the initial reaction involves internal nucleophilic attack by the pyridine nitrogen, control of the pyridine pK, is critical. In this paper we show that by utilizing the powerful electron-donating effect of a 4-amino substituent on the pyridine, moderated ...