Synthesis of 4-(phenylamino)quinoline-3-carboxamides as a novel class of gastric H+/K+-ATPase inhibitors.
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.
Uchida
M
M
Tokushima Research Institute, Japan.
Otsubo
K
K
Matsubara
J
J
Ohtani
T
T
Morita
S
S
Yamasaki
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004355:Drug Stability; D005744:Gastric Acid / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D054328:Proton Pump Inhibitors; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000201:enzymology*; D013276:Stomach Ulcer / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D011804:Quinolines; D017506:H(+)-K(+)-Exchanging ATPase