Terashima K, Tanimura T, Shimamura H, Kawase A, Uenishi K, Tanaka Y, Kimura I, Kamisaki T, Ishizuka Y, Sato M
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Chem Pharm Bull (Tokyo). 1995 Jun;43(6):1042-4. doi: 10.1248/cpb.43.1042.
With the aim of applying mast cell-stabilizing agents as antiulcer agents, N-(1H-tetrazol-5-yl)-2-anilino-5-pyrimidinecarboxamides were synthesized, and initially evaluated pharmacologically for activity in the rat passive cutaneous anaphylaxis test by oral administration. The most active compound 6 was proved to inhibit potently the release of histamine from passively sensitized rat peritoneal mast cells in vitro. When compared with other mast cell-stabilizing agents and an antiulcer agent, compound 6 was found to show excellent gastric mucosal protection and gastric antisecretion activities. Furthermore, compound 6 revealed good activity against acidified aspirin ulcer in rats and water-immersion stress ulcer in rats.
为了将肥大细胞稳定剂用作抗溃疡药物,合成了N-(1H-四唑-5-基)-2-苯胺基-5-嘧啶甲酰胺,并通过口服给药在大鼠被动皮肤过敏试验中对其活性进行了初步药理学评估。最具活性的化合物6在体外被证明能有效抑制被动致敏大鼠腹膜肥大细胞释放组胺。与其他肥大细胞稳定剂和一种抗溃疡药物相比,发现化合物6具有出色的胃黏膜保护和胃泌抑制活性。此外,化合物6对大鼠酸化阿司匹林溃疡和水浸应激溃疡显示出良好的活性。