N-(3-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy)phenyl)-3-(trifluoromethyl)benzenesulfonamide | 1400989-43-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy)phenyl)-3-(trifluoromethyl)benzenesulfonamide
• 英文别名: N-[3-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)oxy]phenyl]-3-(trifluoromethyl)benzenesulfonamide
• CAS: 1400989-43-6
• 化学式: C₂₀H₁₄F₃N₃O₄S
• 分子量: 449.41
• InChiKey: QLCHTWPHPHDIGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  、 3-三氟甲基苯磺酰氯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-(3-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)oxy)phenyl)-3-(trifluoromethyl)benzenesulfonamide
  参考文献：
  名称：

  Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity

  摘要：

  Previously, we demonstrated that the multiple kinase inhibitor sorafenib mediates the repression of phospho-STAT3 in hepatocellular carcinoma cells. In this study, we used this kinase-independent mechanism as a molecular basis to use sorafenib as scaffold to develop a novel class of SHP-1-activating agents. The proof of principle of this premise was provided by SC-1, which on replacement of N-methylpicolinamide by a phenylcyano group showed abolished kinase activity while retaining phospho-STAT3 repressive activity. Structural optimization of SC-1 led to compound 6, which repressed phospho-STAT3 through SHP-1 activation and inhibited PLC5 cell proliferation at sub-micromolar potency. In light of the pivotal role of phospho-STAT3 in promoting tumorigenesis and drug resistance, this novel SHP-1-activating agent may have therapeutic relevance in cancer therapy. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.023

文献信息

• Blockade of STAT3 activation by sorafenib derivatives through enhancing SHP-1 phosphatase activity
  作者：Kuen-Feng Chen、Wei-Tien Tai、Cheng-Yi Hsu、Jui-Wen Huang、Chun-Yu Liu、Pei-Jer Chen、InKi Kim、Chung-Wai Shiau

  DOI：10.1016/j.ejmech.2012.07.023

  日期：2012.9

  Previously, we demonstrated that the multiple kinase inhibitor sorafenib mediates the repression of phospho-STAT3 in hepatocellular carcinoma cells. In this study, we used this kinase-independent mechanism as a molecular basis to use sorafenib as scaffold to develop a novel class of SHP-1-activating agents. The proof of principle of this premise was provided by SC-1, which on replacement of N-methylpicolinamide by a phenylcyano group showed abolished kinase activity while retaining phospho-STAT3 repressive activity. Structural optimization of SC-1 led to compound 6, which repressed phospho-STAT3 through SHP-1 activation and inhibited PLC5 cell proliferation at sub-micromolar potency. In light of the pivotal role of phospho-STAT3 in promoting tumorigenesis and drug resistance, this novel SHP-1-activating agent may have therapeutic relevance in cancer therapy. (C) 2012 Elsevier Masson SAS. All rights reserved.