Nagatomi H, Ando K
Arzneimittelforschung. 1984;34(5):599-603.
A series of derivatives of 4-arylthiazole acetic acid and 2-aminothiazole were studied with respect of their antiinflammatory effect in rat carrageenin edema. Some active compounds were found, which suppressed the paw edema formation strongly, and two compounds were selected, 4-(4-chlorophenyl)-2-phenylaminothiazole acetic acid (Compd. 29) and 4-(4-chlorophenyl)-2-diethylaminothiazole acetic acid (Compd. 71) for further detailed studies. These compounds (Compd. 29 and Compd. 71) moderately inhibited the denaturation of albumin with heat-treatment. Hyperthermic lysis of erythrocytes were strongly inhibited with both Compds. 29 and 71 in the wide range of concentrations (5 X 10(-5) mol/l-5 X 10(-4) mol/l), while their related compound, Compd. 2 (fentiazac) and the reference drugs, ibuprofen, phenylbutazone and flufenamic acid, were either ineffective or stimulatory at the higher concentration. Compds. 29 and 71 inhibited strongly both trypsin and chymotrypsin activities, which differed from the above reference drugs qualitatively and quantitatively. The adverse effect on the gastrointestinal membrane was less with Compd. 29 and Compd. 71 compared with fentiazac and ibuprofen. Compd. 29 especially gave the preferable results with almost no gastric damage at the higher dosage together with its good anti-edematous activity. The characteristics of Compds. 29 and 71 are discussed in terms of the correlation between anti-inflammatory effect and ulcerogenic effect and also of the clinical application.
研究了一系列4-芳基噻唑乙酸和2-氨基噻唑衍生物对大鼠角叉菜胶性水肿的抗炎作用。发现了一些活性化合物，它们能强烈抑制爪部水肿的形成，并选择了两种化合物，即4-(4-氯苯基)-2-苯基氨基噻唑乙酸（化合物29）和4-(4-氯苯基)-2-二乙氨基噻唑乙酸（化合物71）进行进一步详细研究。这些化合物（化合物29和化合物71）适度抑制了热处理引起的白蛋白变性。化合物29和71在很宽的浓度范围内（5×10⁻⁵mol/l - 5×10⁻⁴mol/l）都能强烈抑制红细胞的热溶解，而它们的相关化合物化合物2（芬替酸）以及参比药物布洛芬、保泰松和氟芬那酸在较高浓度时要么无效要么起刺激作用。化合物29和71对胰蛋白酶和糜蛋白酶的活性都有强烈抑制作用，这在定性和定量上都与上述参比药物不同。与芬替酸和布洛芬相比，化合物29和化合物71对胃肠道黏膜的不良影响较小。化合物29尤其给出了较好的结果，在较高剂量时几乎没有胃损伤，同时具有良好的抗水肿活性。从抗炎作用与致溃疡作用的相关性以及临床应用方面讨论了化合物29和化合物71的特性。
