7-((3,4-dichlorophenyl)amino)benzo[b]thiophene-1,1-dioxide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 7-((3,4-dichlorophenyl)amino)benzo[b]thiophene-1,1-dioxide
• 英文别名: N-(3,4-dichlorophenyl)-1,1-dioxo-1-benzothiophen-7-amine
• 化学式: C₁₄H₉Cl₂NO₂S
• 分子量: 326.203
• InChiKey: RMJKHMJHXLSCID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  7-溴-1-苯并噻吩-2-羧酸 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 间氯过氧苯甲酸 、 silver carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 16.0h， 生成 7-((3,4-dichlorophenyl)amino)benzo[b]thiophene-1,1-dioxide
  参考文献：
  名称：

  Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules

  摘要：

  STAT3 is an attractive therapeutic target for cancer therapy. However, due to low potency or poor druggability, none of its inhibitors are clinically available. Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness properties were designed, synthesized and evaluated as STAT3 inhibitors. Most of them exhibited higher antitumor activity than the small-molecule STAT3 inhibitor, Stattic. Compound 15 was the most potent and had an IC50 range in 0.33-0.75 mu M in various cancer cell lines. The overexpressed and IL-6 induced phosphorylation levels of STAT3 were both inhibited by 15 without influencing the phosphorylation levels of the upstream kinases Src and Jak2. 15 also suppressed the expressions of STAT3 downstream gene, Bcl-2. 15 effectively increased the ROS levels of cancer cells, induced cancer cell apoptosis and abolished the colony formation ability of cancer cells without affecting bypass kinase p-Erk. Furthermore, 15 in vivo induced significant antitumor responses, and exhibited less toxicity than Doxorubicin. Together, this study described a class of new STAT3 inhibitors as antitumor agents. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.09.068

文献信息

• Antagonizing STAT3 activation with benzo[b]thiophene 1, 1-dioxide based small molecules
  作者：Wenda Zhang、Ting Ma、Shanshan Li、Yanwei Yang、Jianpeng Guo、Wenying Yu、Lingyi Kong

  DOI：10.1016/j.ejmech.2016.09.068

  日期：2017.1

  STAT3 is an attractive therapeutic target for cancer therapy. However, due to low potency or poor druggability, none of its inhibitors are clinically available. Herein, a series of aminobenzo[b]thiophene 1, 1-dioxides with good drug-likeness properties were designed, synthesized and evaluated as STAT3 inhibitors. Most of them exhibited higher antitumor activity than the small-molecule STAT3 inhibitor, Stattic. Compound 15 was the most potent and had an IC50 range in 0.33-0.75 mu M in various cancer cell lines. The overexpressed and IL-6 induced phosphorylation levels of STAT3 were both inhibited by 15 without influencing the phosphorylation levels of the upstream kinases Src and Jak2. 15 also suppressed the expressions of STAT3 downstream gene, Bcl-2. 15 effectively increased the ROS levels of cancer cells, induced cancer cell apoptosis and abolished the colony formation ability of cancer cells without affecting bypass kinase p-Erk. Furthermore, 15 in vivo induced significant antitumor responses, and exhibited less toxicity than Doxorubicin. Together, this study described a class of new STAT3 inhibitors as antitumor agents. (C) 2016 Elsevier Masson SAS. All rights reserved.