4-(bromomethyl)-N-{(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)thio]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}benzenesulfonamide | 741671-76-1

• 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: 4-(bromomethyl)-N-{(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)thio]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}benzenesulfonamide
• 英文别名: 4-(bromomethyl)-N-[5,6-dimethyl-3-oxo-8-(4,4,5,5,5-pentafluoropentylsulfanyl)imidazo[5,1-c][1,4]thiazin-1-yl]benzenesulfonamide
• CAS: 741671-76-1
• 化学式: C₂₀H₁₉BrF₅N₃O₃S₃
• 分子量: 620.483
• InChiKey: GLXPWLJDJDPYOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-(bromomethyl)-N-{(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)thio]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}benzenesulfonamide 在 sodium iodide 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以16%的产率得到N-{(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)thio]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}-4-(iodometyl)benzenesulfonamide
  参考文献：
  名称：

  ITZ-1, a Client-Selective Hsp90 Inhibitor, Efficiently Induces Heat Shock Factor 1 Activation

  摘要：

  ITZ-1 is a chondroprotective agent that inhibits interleukin-1 beta-induced matrix metalloproteinase-13 (MMP-13) production and suppresses nitric oxide-induced chondrocyte death. Here we describe its mechanisms of action. Heat shock protein 90 (Hsp90) was identified as a specific ITZ-1-binding protein. Almost all known Hsp90 inhibitors have been reported to bind to the Hsp90 N-terminal ATP-binding site and to simultaneously induce degradation and activation of its multiple client proteins. However, within the Hsp90 client proteins, ITZ-1 strongly induces heat shock factor-1 (HSF1) activation and causes mild Raf-1 degradation, but scarcely induces degradation of a broad range of Hsp90 client proteins by binding to the Hsp90 C terminus. These results may explain ITZ-1's inhibition of MMP-13 production, its cytoprotective effect, and its lower cytotoxicity. These results suggest that ITZ-1 is a client-selective Hsp90 inhibitor.

  DOI：

  10.1016/j.chembiol.2009.12.012
• 作为产物：
  描述：

  1-amino-5,6-dimethyl-8-[(4,4,5,5,5-pentafluoropentyl)thio]-3H-imidazo[5,1-c][1,4]thiazin-3-one 、 4-溴甲基苯磺酰氯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 15.08h， 以63%的产率得到4-(bromomethyl)-N-{(1Z)-5,6-dimethyl-3-oxo-8-[(4,4,5,5,5-pentafluoropentyl)thio]-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}benzenesulfonamide
  参考文献：
  名称：

  ITZ-1, a Client-Selective Hsp90 Inhibitor, Efficiently Induces Heat Shock Factor 1 Activation

  摘要：

  ITZ-1 is a chondroprotective agent that inhibits interleukin-1 beta-induced matrix metalloproteinase-13 (MMP-13) production and suppresses nitric oxide-induced chondrocyte death. Here we describe its mechanisms of action. Heat shock protein 90 (Hsp90) was identified as a specific ITZ-1-binding protein. Almost all known Hsp90 inhibitors have been reported to bind to the Hsp90 N-terminal ATP-binding site and to simultaneously induce degradation and activation of its multiple client proteins. However, within the Hsp90 client proteins, ITZ-1 strongly induces heat shock factor-1 (HSF1) activation and causes mild Raf-1 degradation, but scarcely induces degradation of a broad range of Hsp90 client proteins by binding to the Hsp90 C terminus. These results may explain ITZ-1's inhibition of MMP-13 production, its cytoprotective effect, and its lower cytotoxicity. These results suggest that ITZ-1 is a client-selective Hsp90 inhibitor.

  DOI：

  10.1016/j.chembiol.2009.12.012