Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase.

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Adelstein GW, Yen CH, Haack RA, Yu S, Gullikson G, Price DV, Anglin C, Decktor DL, Tsai H, Keith RH

Substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines as potential inhibitors of H+/K+ ATPase.

J Med Chem. 1988 Jun;31(6):1215-20.

PubMed ID

2836591 [ View in PubMed

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Abstract

A series of substituted 2-[(2-benzimidazolylsulfinyl)methyl]anilines were synthesized as potential inhibitors of the acid secretory enzyme H+/K+ ATPase. Substitutions on the aniline nitrogen atom resulted in potent enzyme inhibition in vitro but weak activity in gastric fistula dogs. Electron-donating substituents on the aniline ring enhanced in vitro and in vivo potency relative to the unsubstituted analogue. The potency showed a correlation to the calculated pKa of the aniline nitrogen atom. Substitutions on the aniline and benzimidazole rings did not further enhance potency. Di- and trisubstituted aniline derivatives were potent inhibitors of the enzyme system. The preferred combination of substituents were a methoxy group on the benzimidazole ring and a single alkyl group on the aniline ring. One such compound, 76, was an effective inhibitor of acid secretion in the dog and was selected for further pharmacological study.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Omeprazole	Potassium-transporting ATPase alpha chain 1	IC 50 (nM)	2000	N/A	N/A	Details