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):1077-87. doi: 10.1016/s0968-0896(98)00066-2.
A series of m-bis(glycoloylamino)benzene derivatives was synthesized by treatment of the corresponding m-diaminobenzene derivatives with glycoloyl chloride derivatives in pyridine. Hydrolysis of acetyl compounds gave hydroxy derivatives, from which other acyl derivatives could be synthesized. These compounds were tested in the rat PCA (passive cutaneous anaphylaxis) assay by oral administration. Benzonitrile derivatives (4c, 5c, 6c, 4h, 5h) exhibited notable inhibition in this assay. Compounds 5c and 6c also showed remarkable 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. Compound 5c is now under investigation in Japan as TYB-2285 (Figure 1) for asthma and atopic dermatitis in phase II clinical studies.
通过在吡啶中用乙醇酰氯衍生物处理相应的间二氨基苯衍生物，合成了一系列间双（乙醇酰氨基）苯衍生物。乙酰化合物的水解产生羟基衍生物，由此可以合成其他酰基衍生物。通过口服给药在大鼠PCA（被动皮肤过敏反应）试验中对这些化合物进行了测试。苯甲腈衍生物（4c、5c、6c、4h、5h）在此试验中表现出显著的抑制作用。化合物5c和6c在10（-8）-10（-5）M范围内也对嗜酸性粒细胞黏附于经肿瘤坏死因子α处理的人脐静脉内皮细胞表现出显著抑制作用。化合物5c目前在日本作为TYB-2285（图1）正在进行II期临床研究，用于治疗哮喘和特应性皮炎。
