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

• Published in: Chemical & pharmaceutical bulletin Vol. 43; no. 1; pp. 166 - 168
• Main Authors: 寺島 幸司, 嶋村 浩, 川瀬 明人, 田中 裕二, 上西 啓司, 木村 伊佐美, 石塚 泰博, 佐藤 誠
• Format: Journal Article
• Language: English
• Published: The Pharmaceutical Society of Japan 01.01.1995; 公益社団法人日本薬学会
• Subjects: antisecretion; antiulcer agent; H; K^+-ATPase inhibitor; mucosal protection; pyrimidine derivative
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.43.166

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.