Reversible inhibitors of the gastric (H+/K+)-ATPase. 2. 1-Arylpyrrolo[3,2-c]quinolines: effect of the 4-substituent.
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.
Leach
C A
CA
SmithKline Beecham Pharmaceuticals R&D, Welwyn, Herts, England.
Brown
T H
TH
Ife
R J
RJ
Keeling
D J
DJ
Laing
S M
SM
Parsons
M E
ME
Price
C A
CA
Wiggall
K J
KJ
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004789:Enzyme Activation; D017506:H(+)-K(+)-Exchanging ATPase; D009682:Magnetic Resonance Spectroscopy; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000201:enzymology*
D000634:Aminoquinolines; C069657:1-(2-methylphenyl)-4-methylamino-6-methyl-2,3-dihydropyrrolo(3,2-c)quinoline; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D010418:Pentagastrin