ethyl (1Z)-8-[-3-(ethoxy-3-oxopropyl)thio]-5-hydroxy-5-methyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3,5,6-tetrahydro-1H-imidazo[5,1-c][1,4]thiazine-6-carboxylate | 476413-21-5

• 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: ethyl (1Z)-8-[-3-(ethoxy-3-oxopropyl)thio]-5-hydroxy-5-methyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3,5,6-tetrahydro-1H-imidazo[5,1-c][1,4]thiazine-6-carboxylate
• CAS: 476413-21-5
• 化学式: C₂₂H₂₇N₃O₈S₃
• 分子量: 557.67
• InChiKey: MUVKWTGQDSZZOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.35
• 重原子数：
  36.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  151.67
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  ethyl (1Z)-8-[-3-(ethoxy-3-oxopropyl)thio]-5-hydroxy-5-methyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3,5,6-tetrahydro-1H-imidazo[5,1-c][1,4]thiazine-6-carboxylate 在 左旋樟脑磺酸 作用下， 以 甲苯 为溶剂， 以76%的产率得到ethyl (1Z)-8-[(3-ethoxy-3-oxopropyl)thio]-5-methyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazine-6-carboxylate
  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：

  ethyl 3-{[(E)-mercapto((5Z)-5-{[(4-methylphenyl)sulfonyl]imino}-2-oxoimidazolidin-4-ylidene)methyl]thio}propanoate 、 2-氯乙酰乙酸乙酯 在 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到ethyl (1Z)-8-[-3-(ethoxy-3-oxopropyl)thio]-5-hydroxy-5-methyl-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3,5,6-tetrahydro-1H-imidazo[5,1-c][1,4]thiazine-6-carboxylate
  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