Synthesis of 4-(phenylamino)quinoline-3-carboxamides as a Novel Class of Gastric H⁺/K⁺-ATPase Inhibitors

Abstract

In a 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.