Ban M, Taguchi H, Katsushima T, Takahashi M, Shinoda K, Watanabe A, Tominaga T
Pharmaceuticals Research Center, TOYOBO Co., Ltd, Ohtsu, Shiga, Japan.
Bioorg Med Chem. 1998 Jul;6(7):1069-76. doi: 10.1016/s0968-0896(98)00065-0.
A series of mono-glycoloylamino derivatives was synthesized by treatment of the corresponding aromatic monoamine derivatives with glycoloyl chloride derivatives in pyridine or dichloromethane, in the presence of a base such as triethylamine or pyridine. Hydrolysis of acetoxy compounds in aqueous ammonia and methanol solution produced hydroxy derivatives with ease. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Thiazole and thiadiazole derivatives showed moderate inhibition in this assay. In contrast, benzothiazole and benzonitrile derivatives exhibited marked inhibition. In particular, compound 5t also showed marked inhibition of eosinophil adhesion to TNF (tumor necrosis factor) -alpha-treated HUVEC (human umbilical vein endothelial cells) in the range of 10(-8)-10(-5) M.
通过在吡啶或二氯甲烷中，在三乙胺或吡啶等碱的存在下，用乙醇酰氯衍生物处理相应的芳族单胺衍生物，合成了一系列单乙醇酰氨基衍生物。乙酰氧基化合物在氨水溶液和甲醇溶液中易于水解生成羟基衍生物。通过口服给药在大鼠PCA（被动皮肤过敏反应）试验中测试了这些化合物。噻唑和噻二唑衍生物在该试验中显示出中等程度的抑制作用。相比之下，苯并噻唑和苯甲腈衍生物表现出明显的抑制作用。特别地，化合物5t在10(-8)-10(-5)M范围内也显示出对嗜酸性粒细胞粘附于TNF（肿瘤坏死因子）-α处理的HUVEC（人脐静脉内皮细胞）的明显抑制作用。
