Reversible Inhibitors of the Gastric (H+/K+)-ATPase. 2. 1-Arylpyrrolo[3,2-c]quinolines: Effect of the 4-substituent

J Med Chem. 1992 May 15;35(10):1845-52. doi: 10.1021/jm00088a021.

Abstract

Further work on compounds 1 has identified the 4-position as a site where substantial modifications are tolerated, leading to analogues which are more potent and less toxic than those described previously. The best compound in the series is 13a (SK&F 96356), which is a potent inhibitor of gastric acid secretion in both the pentagastrin-stimulated rat and the histamine-stimulated dog. This compound shows reversible, K(+)-competitive binding to the enzyme. Because of its fluorescent properties, it is also proving useful in vitro as a probe of the structure and function of the (H+/K+)-ATPase.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / metabolism
  • Aminoquinolines / pharmacology*
  • Animals
  • Dogs
  • Enzyme Activation
  • H(+)-K(+)-Exchanging ATPase
  • Magnetic Resonance Spectroscopy
  • Pentagastrin / pharmacology
  • Rats
  • Stomach / enzymology*

Substances

  • Aminoquinolines
  • 1-(2-methylphenyl)-4-methylamino-6-methyl-2,3-dihydropyrrolo(3,2-c)quinoline
  • Adenosine Triphosphatases
  • H(+)-K(+)-Exchanging ATPase
  • Pentagastrin