(1Z)-8-[(3-methylbutyl)thio]-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazine-5-carboxylic acid | 476426-24-1

• 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: (1Z)-8-[(3-methylbutyl)thio]-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazine-5-carboxylic acid
• 英文别名: ITZ-12；8-(3-Methylbutylsulfanyl)-1-[(4-methylphenyl)sulfonylamino]-3-oxoimidazo[5,1-c][1,4]thiazine-5-carboxylic acid；8-(3-methylbutylsulfanyl)-1-[(4-methylphenyl)sulfonylamino]-3-oxoimidazo[5,1-c][1,4]thiazine-5-carboxylic acid
• CAS: 476426-24-1
• 化学式: C₁₉H₂₁N₃O₅S₃
• 分子量: 467.591
• InChiKey: KTZMXZPVFCPUFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  175
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ethyl (1Z)-8-[(3-methylbutyl)thio]-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazine-5-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 以82%的产率得到(1Z)-8-[(3-methylbutyl)thio]-1-{[(4-methylphenyl)sulfonyl]imino}-3-oxo-2,3-dihydro-1H-imidazo[5,1-c][1,4]thiazine-5-carboxylic acid
  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

文献信息

• ITZ-1, a Client-Selective Hsp90 Inhibitor, Efficiently Induces Heat Shock Factor 1 Activation
  作者：Haruhide Kimura、Hiroshi Yukitake、Yasukazu Tajima、Hirobumi Suzuki、Tomoko Chikatsu、Shinji Morimoto、Yasunori Funabashi、Hiroaki Omae、Takashi Ito、Yukio Yoneda、Masayuki Takizawa

  DOI：10.1016/j.chembiol.2009.12.012

  日期：2010.1

  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.