N-{3-[(1-amino-5,6-dimethyl-3-oxo-3H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}hexanamide | 476421-69-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-{3-[(1-amino-5,6-dimethyl-3-oxo-3H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}hexanamide
• 英文别名: N-[3-(1-amino-5,6-dimethyl-3-oxoimidazo[5,1-c][1,4]thiazin-8-yl)sulfanylpropyl]hexanamide
• CAS: 476421-69-9
• 化学式: C₁₇H₂₆N₄O₂S₂
• 分子量: 382.551
• InChiKey: NDHZFZBAUAKFGP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-{3-[(1-amino-5,6-dimethyl-3-oxo-3H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}hexanamide 、 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69%的产率得到N-(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)hexanamide
  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：

  N-{3-[((1Z)-5,6-dimethyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}hexanamide 在 甲酸铵 作用下， 以 乙醇 为溶剂， 以65%的产率得到N-{3-[(1-amino-5,6-dimethyl-3-oxo-3H-imidazo[5,1-c][1,4]thiazin-8-yl)thio]propyl}hexanamide
  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