Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds
Novel antiallergic and antiinflammatory agents. Part II: Synthesis and pharmacology of TYB-2285 and its related compounds
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DOI：
10.1016/s0968-0896(98)00066-2
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发表时间：
1998-07-01
影响因子：
3.5
通讯作者：
Tominaga, T
中科院分区：
文献类型：
--
作者：
Ban, M;Taguchi, H;Tominaga, T
以间苯二胺为原料，在吡啶溶剂中与乙醇酰氯反应，合成了一系列间苯二胺衍生物。乙酰基化合物水解得到羟基衍生物，由羟基衍生物可以合成其他酰基衍生物。这些化合物在大鼠PCA（被动皮肤过敏反应）试验中通过口服给药进行了测试。苯甲腈衍生物（4c、5c、6c、4 h、5 h）在本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范围内也显示出显著抑制嗜酸性粒细胞粘附到TNF-（肿瘤坏死因子）α处理的HUVEC（人脐静脉内皮细胞）。化合物5c目前正在日本作为TYB-2285（图1）进行II期临床研究，用于哮喘和特应性皮炎。(C)1998爱思唯尔科技有限公司版权所有。
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. (C) 1998 Elsevier Science Ltd. All rights reserved.