Katsura Y, Inoue Y, Tomishi T, Ishikawa H, Takasugi H
New Drug Research Laboratories, Fujisawa Pharmaceutical Company, Limited, Osaka, Japan.
J Med Chem. 1994 Jan 7;37(1):57-66. doi: 10.1021/jm00027a007.
A series of 2-guanidino-4-pyridylthiazole derivatives were synthesized and evaluated for anti-aspirin-ulcer, gastric antisecretory, and histamine-H2-receptor-antagonist activities. Several compounds showed superior anti-aspirin-ulcer activity to that of clinically used H2-antagonists in the rat. Among them, 4-[6-(acetamidomethyl)pyridin-2-yl]-2-guanidinothiazole (8) demonstrated potent inhibitory activities against gastric lesions caused by two kinds of nonsteroidal antiinflammatory drugs, aspirin and indomethacin, respectively, in addition to strong antisecretory activity. Compound 8 possessed a preventable ability for the aspirin-induced reduction of the gastric mucosal blood flow at an intragastric administration of 32 mg/kg in the rat. On the other hand, famotidine (32 mg/kg) exhibited no significant effect and ranitidine (100 mg/kg) aggravated the blood flow in this system.
合成了一系列2-胍基-4-吡啶基噻唑衍生物，并对其抗阿司匹林溃疡、胃泌酸抑制及组胺H2受体拮抗活性进行了评估。在大鼠中，几种化合物表现出优于临床使用的H2拮抗剂的抗阿司匹林溃疡活性。其中，4-[6-(乙酰氨基甲基)吡啶-2-基]-2-胍基噻唑(8)除具有较强的泌酸抑制活性外，还分别对两种非甾体抗炎药阿司匹林和吲哚美辛引起的胃损伤表现出强效抑制活性。在大鼠胃内给药32mg/kg时，化合物8具有预防阿司匹林引起的胃黏膜血流量减少的能力。另一方面，法莫替丁(32mg/kg)无显著作用，雷尼替丁(100mg/kg)则使该系统中的血流量增加。
