Synthesis of 4-(phenylamino)quinoline-3-carboxamides as a novel class of gastric H+/K+-ATPase inhibitors

Chem Pharm Bull (Tokyo). 1995 Apr;43(4):693-8. doi: 10.1248/cpb.43.693.

Abstract

In search for inhibitors of gastric H+/K+-ATPase, 4-(phenylamino)quinoline-3-carboxamides were synthesized and evaluated for antisecretory activity against histamine-induced gastric acid secretion in rats. These compounds were synthesized by condensation of aniline derivatives with N-substituted 4-chloroquinoline-3-carboxamides, which were obtained from treatment of 4(1H)-quinolinone-3-carboxylic acid with thionyl chloride. Most of the compounds inhibited histamine-induced gastric acid secretion in rats. Among them, N-allyl-4-(2-ethylphenylamino)quinoline-3-carboxamide (4h) was the most potent inhibitor and had the best profile as a candidate antiulcer agent. This compound showed reversible, K+-competitive gastric H+/K+-ATPase inhibitory activity.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis*
  • Anti-Ulcer Agents / chemistry
  • Anti-Ulcer Agents / pharmacology
  • Drug Stability
  • Gastric Acid / metabolism
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Kinetics
  • Male
  • Proton Pump Inhibitors*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Rats
  • Rats, Wistar
  • Stomach / enzymology*
  • Stomach Ulcer / prevention & control

Substances

  • Anti-Ulcer Agents
  • Proton Pump Inhibitors
  • Quinolines
  • H(+)-K(+)-Exchanging ATPase