| Autor: |
Brown TH; Department of Medicinal Chemistry, Smith Kline & French Research Ltd., Welwyn, Herts, England., Ife RJ, Keeling DJ, Laing SM, Leach CA, Parsons ME, Price CA, Reavill DR, Wiggall KJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1990 Feb; Vol. 33 (2), pp. 527-33. |
| DOI: |
10.1021/jm00164a010 |
| Abstrakt: |
The 4-(arylamino)quinoline 4, previously described as an antiulcer compound, is shown to be an inhibitor of the gastric (H+/K+)-ATPase. It is postulated that 1-arylpyrrolo[3,2-c]quinolines 6 act as conformationally restrained analogues of 4. A series of derivatives of 6 has been prepared and shown to be potent inhibitors of the target enzyme in vitro. Substitution in the ortho position of the aryl ring is important for activity. Unsaturation in the 5-membered ring makes little difference, but introduction of heteroatoms into the same ring markedly reduces activity. In more detailed kinetic experiments, 15c and 4 both show reversible, K(+)-competitive binding to the enzyme, with submicromolar Ki values. The compounds appear to act at the lumenal face of the enzyme and to require protonation for activity. Several compounds in the series are shown to be potent inhibitors of pentagastrin-stimulated acid secretion in the rat. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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