tert-butyl (3-{[(1Z)-1-({[4-(acetylamino)phenyl]sulfonyl}imino)-5,6-dimethyl-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl]thio}propyl)carbamate | 476423-23-1

• 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: tert-butyl (3-{[(1Z)-1-({[4-(acetylamino)phenyl]sulfonyl}imino)-5,6-dimethyl-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl]thio}propyl)carbamate
• 英文别名: tert-butyl N-[3-[1-[(4-acetamidophenyl)sulfonylamino]-5,6-dimethyl-3-oxoimidazo[5,1-c][1,4]thiazin-8-yl]sulfanylpropyl]carbamate
• CAS: 476423-23-1
• 化学式: C₂₄H₃₁N₅O₆S₃
• 分子量: 581.738
• InChiKey: JPJFOQNNDAAJMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  205
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (3-{[(1Z)-1-({[4-(acetylamino)phenyl]sulfonyl}imino)-5,6-dimethyl-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl]thio}propyl)carbamate 在 三氟乙酸 作用下， 生成 N-{4-[({(1Z)-8-[(3-aminopropyl)thio]-5,6-dimethyl-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-1-ylidene}amino)sulfonyl]phenyl}acetamide
  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：

  tert-butyl {3-[(1-amino-5,6-dimethyl-3-oxo-3H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}carbamate 、 对乙酰胺基苯磺酰氯 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 以61%的产率得到tert-butyl (3-{[(1Z)-1-({[4-(acetylamino)phenyl]sulfonyl}imino)-5,6-dimethyl-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl]thio}propyl)carbamate
  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