N-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl]-N-[12-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl-(4-nitrophenyl)sulfonylamino]dodecyl]-4-nitrobenzenesulfonamide | 1043569-29-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl]-N-[12-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl-(4-nitrophenyl)sulfonylamino]dodecyl]-4-nitrobenzenesulfonamide
• CAS: 1043569-29-4
• 化学式: C₆₆H₈₀N₁₄O₁₄S₂
• 分子量: 1357.58
• InChiKey: QKACPNRJYGZJAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.6
• 重原子数：
  96
• 可旋转键数：
  35
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  378
• 氢给体数：
  2
• 氢受体数：
  24

反应信息

• 作为反应物：
  描述：

  N-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl]-N-[12-[6-[6-amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-ynyl-(4-nitrophenyl)sulfonylamino]dodecyl]-4-nitrobenzenesulfonamide 在 potassium carbonate 、 苯硫酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 PU3-C12-dimer
  参考文献：
  名称：

  Synthesis of Hsp90 inhibitor dimers as potential antitumor agents

  摘要：

  Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.04.070
• 作为产物：
  描述：

  6-[6-Amino-8-[(3,4,5-trimethoxyphenyl)methyl]purin-9-yl]hex-2-yn-1-ol 、 N,N'-di-(4-nitrobenzenesulfonyl)-1,12-diaminododecane 在 Bu₃P=CHCN 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以41%的产率得到
  参考文献：
  名称：

  Synthesis of Hsp90 inhibitor dimers as potential antitumor agents

  摘要：

  Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.04.070

文献信息

• Synthesis of Hsp90 inhibitor dimers as potential antitumor agents
  作者：Kazuhiro Muranaka、Akiko Sano、Satoshi Ichikawa、Akira Matsuda

  DOI：10.1016/j.bmc.2008.04.070

  日期：2008.6

  Structure-based drug design was used to systematically synthesize PU3-dimers. The cytotoxicity of PU3 dimers 6 against breast cancer cell lines was evaluated, and their potency increased as the length of the bridging linker increased. Among the compounds tested, 6e with a C-20 linker was the most potent and exhibited a 20- to 30-fold increase in activity compared with that of the parent compound 5. Western blot analyses of the cell lysates treated with 6c revealed that 6c resulted in the concentration-dependent degradation of the Hsp90 client protein Her2, which is consistent with other Hsp90 inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.