GMD-C4-dimer

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: GMD-C4-dimer
• 英文别名: [(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-19-[4-[[(4E,6Z,8S,9S,10E,12S,13R,14S,16R)-9-carbamoyloxy-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-19-yl]amino]butylamino]-13-hydroxy-8,14-dimethoxy-4,10,12,16-tetramethyl-3,20,22-trioxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,18-pentaen-9-yl] carbamate
• 化学式: C₆₀H₈₄N₆O₁₆
• 分子量: 1145.36
• InChiKey: GAKXGNSPLDCQIF-DOFJNMHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  82
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  333
• 氢给体数：
  8
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  四亚甲基二胺 、 格尔德霉素 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以90%的产率得到GMD-C4-dimer
  参考文献：
  名称：

  Synthesis of Hsp90 dimerization modulators

  摘要：

  The synthesis and evaluation of several chemical modulators of heat shock protein 90 (Hsp90) dimerization is presented. These agents may represent useful tools to study the importance of N-terminal dimerization and also to determine subunit interface(s) in Hsp90. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.03.092

文献信息

• Synthesis of Hsp90 dimerization modulators
  作者：Gabriela Chiosis、Julia Aguirre、Christopher V. Nicchitta

  DOI：10.1016/j.bmcl.2006.03.092

  日期：2006.7

  The synthesis and evaluation of several chemical modulators of heat shock protein 90 (Hsp90) dimerization is presented. These agents may represent useful tools to study the importance of N-terminal dimerization and also to determine subunit interface(s) in Hsp90. (c) 2006 Elsevier Ltd. All rights reserved.
• US7271160B2
  申请人：——

  公开号：US7271160B2

  公开（公告）日：2007-09-18
• 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.