Studies on antiulcer agents. I. Synthesis and pharmacological properties of ethyl 2-[(1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate, a new H+/K(+)-ATPase inhibitor possessing mucosal protective activity.
Ethyl 2-[1H-benzimidazol-2-yl)sulfinylmethyl]-4-dimethylamino-5- pyrimidinecarboxylate (2) has been synthesized and evaluated for antiulcer properties. Compound 2 is a H+/K(+)-ATPase inhibitor that affords mucosal protection against absolute ethanol-induced gastric lesions in rats after oral and parenteral administrations. On the other hand, omeprazole, a representative H+/K(+)-ATPase inhibitor, showed mucosal protective action only after oral administration, indicating that it required gastric acid secretion to generate activity. The antiulcer activity of 2 in animal models, such as water-immersion stress-induced gastric ulcer in rats and acidified aspirin-induced gastric ulcer in rats, was three times higher than that of cimetidine.
Terashima
K
K
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Shimamura
H
H
Kawase
A
A
Tanaka
Y
Y
Uenishi
K
K
Kimura
I
I
Ishizuka
Y
Y
Sato
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D010437:Peptic Ulcer / Q000201:enzymology / Q000517:prevention & control*; D054328:Proton Pump Inhibitors; D051381:Rats
D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; C092689:ethyl 2-((1H-benzimidazol-2-yl)sulfinylmethyl)-4-dimethylamino-5-pyrimidinecarboxylate; D017506:H(+)-K(+)-Exchanging ATPase