Studies on antiulcer agents. IV. Antiulcer effects of 2-benzylthio5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds.
With a view to finding more effective antiulcer agents, a series of 2-benzylthio-5,6,7,8-tetrahydro-4(3H)-quinazolinones and related compounds were synthesized and evaluated in a histamine-stimulated gastric secretion model. The sodium salt of the 2-(dimethylamino)benzylthio derivative (8) showed gastric mucosal protection and gastric antisecretion activities, and was also effective against experimental gastric and duodenal ulcers induced by some ulcerogenic agents. Based on a comparison of the antiulcer properties of 8 with those of the lead compounds (1 and 2) and cimetidine, it appears that, for improvement of antiulcer activity, the reduction of gastric acidity is a more important factor than the reduction of gastric volume output or gastric total acid output.
Terashima
K
K
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Shimamura
H
H
Kawase
A
A
Tanaka
Y
Y
Tanimura
T
T
Kamisaki
T
T
Ishizuka
Y
Y
Sato
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000008:administration & dosage / Q000633:toxicity; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004381:Duodenal Ulcer / Q000188:drug therapy; D004840:Epirizole / Q000008:administration & dosage / Q000633:toxicity; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000293:injuries; D006632:Histamine / Q000008:administration & dosage / Q000633:toxicity; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D011799:Quinazolines; D004840:Epirizole; D000431:Ethanol; D002927:Cimetidine; D006632:Histamine; D001241:Aspirin; D007213:Indomethacin