title: Reversible inhibitors of the gastric (H+/K+)-ATPase. 2. 1-Arylpyrrolo[3,2-c]quinolines: effect of the 4-substituent.
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.
authors.affiliation: SmithKline Beecham Pharmaceuticals R&D, Welwyn, Herts, England.
authors.forename: C A
authors.initials: CA
authors.lastname: Leach
authors.forename: T H
authors.initials: TH
authors.lastname: Brown
authors.forename: R J
authors.initials: RJ
authors.lastname: Ife
authors.forename: D J
authors.initials: DJ
authors.lastname: Keeling
authors.forename: S M
authors.initials: SM
authors.lastname: Laing
authors.forename: M E
authors.initials: ME
authors.lastname: Parsons
authors.forename: C A
authors.initials: CA
authors.lastname: Price
authors.forename: K J
authors.initials: KJ
authors.lastname: Wiggall
mesh_terms: 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*
chemical_list: 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