5-bromo-N-phenyl-1-benzothiophene-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 5-bromo-N-phenyl-1-benzothiophene-2-carboxamide
• 化学式: C₁₅H₁₀BrNOS
• 分子量: 332.221
• InChiKey: DUJHHTZZQBYBIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  19
• 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：
  57.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-N-phenyl-1-benzothiophene-2-carboxamide 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以27%的产率得到5-bromo-N-phenylbenzo[b]thiophene-2-carboxamide 1,1-dioxide
  参考文献：
  名称：

  Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway

  摘要：

  Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.

  DOI：

  10.1021/acsmedchemlett.5b00228
• 作为产物：
  描述：

  5-溴-2-氟苯甲醛 在 甲醇 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium hydroxide 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 5-bromo-N-phenyl-1-benzothiophene-2-carboxamide
  参考文献：
  名称：

  Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway

  摘要：

  Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.

  DOI：

  10.1021/acsmedchemlett.5b00228

文献信息

• Novel 2-Carbonylbenzo[<i>b</i>]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway
  作者：Peng Ji、Xin Xu、Shuhua Ma、Junchao Fan、Qiang Zhou、Xinliang Mao、Chunhua Qiao

  DOI：10.1021/acsmedchemlett.5b00228

  日期：2015.9.10

  Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.