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

Chem Pharm Bull (Tokyo). 1995 Jan;43(1):166-8. doi: 10.1248/cpb.43.166.

Abstract

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.

MeSH terms

  • Animals
  • Anti-Ulcer Agents / chemical synthesis*
  • Anti-Ulcer Agents / pharmacology
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology
  • Dogs
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / enzymology
  • H(+)-K(+)-Exchanging ATPase / metabolism
  • Peptic Ulcer / enzymology
  • Peptic Ulcer / prevention & control*
  • Proton Pump Inhibitors*
  • Rats

Substances

  • Anti-Ulcer Agents
  • Benzimidazoles
  • Proton Pump Inhibitors
  • ethyl 2-((1H-benzimidazol-2-yl)sulfinylmethyl)-4-dimethylamino-5-pyrimidinecarboxylate
  • H(+)-K(+)-Exchanging ATPase