2-((2-Pyridylmethyl)sulfinyl)benzimidazoles: acid sensitive suicide inhibitors of the proton transport system in the parietal cell.
2-((2-Pyridylmethyl)sulfinyl)benzimidazoles, selective inhibitors of the H+/K+-ATPase in the parietal cells of the stomach, have been investigated concerning their chemical behaviour in acidic medium. Protonation of the sulfoxide and subsequent elimination of water forms a sulfenium ion or a chemical equivalent thereof. If no external nucleophiles are present, a rearrangement process takes place. In the presence of mercaptans, the sulfenium ion is trapped giving rise to a variety of products. On the basis of these results, a mechanistic scheme is proposed for the inactivation of the H+/K+-ATPase by these compounds.
Rackur
G
G
Bickel
M
M
Fehlhaber
H W
HW
Herling
A
A
Hitzel
V
V
Lang
H J
HJ
Rösner
M
M
Weyer
R
R
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase; D008956:Models, Chemical; D010295:Parietal Cells, Gastric / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology*
D001562:Benzimidazoles; D011725:Pyridines; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase