新型HuR抑制剂1-苯磺酰基-3-苯基吲哚-4,5-二酮的合成

HuR inhibitor: synthesis of 1-phenylsulfonyl-3-phenyl indole-4,5-dione

1-苯磺酰基-3-苯基吲哚-4,5-二酮是一种有效的HuR抑制剂.HuR作为一种应激反应蛋白,可调节编码炎症和肿瘤发生的蛋白质靶基因的表达,是潜在的药物靶点.以5-甲氧基吲哚为起始原料,5-甲氧基吲哚的C-3位与芳基卤化物芳基化,再用苯磺酰氯处理制备1-苯磺酰基-3-苯基吲哚,最后经去甲基化和氧化,共4步反应合成1-苯磺酰基-3-苯基吲哚-4,5-二酮.产物结构经~1H NMR、C NMR进行确证.此合成路线具有合成方法简单,反应时间短,操作简单等优点.

1-phenylsulfonyl-3-phenyl indole-4,5-dione is an effective HuR inhibitor. HuR, as a stress response protein, can regulate the expression of protein target genes encoding inflammation and tumorigenesis, and is a potential drug target. In order to optimize the synthetic route, taking 5-methoxyindole as the raw materials, arylation of 5-methoxyindole at C-3 position and aryl halides, treating with benzenesulfonyl chloride to afford 1-phenylsulfonyl-3-phenylindole, After demethylation and oxidation, the synthesis gradually went through the following four-step reaction. The structures were confirmed by ~1H NMR,C NMR analysis. This synthetic route has the advantages of simple synthetic route, short reaction time and simple operation.