4-{(3aR,4R,6R,6aR)-6-[6-amino-8-(3,4-dichlorobenzylamino)purin-9-yl]-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-ylmethoxymethyl}benzonitrile | 1134156-55-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 4-{(3aR,4R,6R,6aR)-6-[6-amino-8-(3,4-dichlorobenzylamino)purin-9-yl]-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-ylmethoxymethyl}benzonitrile
• 英文别名: 4-[[(3aR,4R,6R,6aR)-4-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxymethyl]benzonitrile
• CAS: 1134156-55-0
• 化学式: C₂₈H₂₇Cl₂N₇O₄
• 分子量: 596.473
• InChiKey: LIRPFRXGUPJXIT-HUBRGWSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-{(3aR,4R,6R,6aR)-6-[6-amino-8-(3,4-dichlorobenzylamino)purin-9-yl]-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-ylmethoxymethyl}benzonitrile 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 3.0h， 以59%的产率得到VER155008抑制剂
  参考文献：
  名称：

  Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design

  摘要：

  The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

  DOI：

  10.1021/jm801627a
• 作为产物：
  描述：

  8-溴-5'-O-[(4-氰基苯基)甲基]-2',3'-O-(异丙亚基)腺苷 、 3,4-二氯苄胺 以 乙醇 为溶剂， 反应 2.0h， 以74%的产率得到4-{(3aR,4R,6R,6aR)-6-[6-amino-8-(3,4-dichlorobenzylamino)purin-9-yl]-2,2-dimethyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-ylmethoxymethyl}benzonitrile
  参考文献：
  名称：

  Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design

  摘要：

  The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.

  DOI：

  10.1021/jm801627a

文献信息

• Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design
  作者：Douglas S. Williamson、Jenifer Borgognoni、Alexandra Clay、Zoe Daniels、Pawel Dokurno、Martin J. Drysdale、Nicolas Foloppe、Geraint L. Francis、Christopher J. Graham、Rob Howes、Alba T. Macias、James B. Murray、Rachel Parsons、Terry Shaw、Allan E. Surgenor、Lindsey Terry、Yikang Wang、Mike Wood、Andrew J. Massey

  DOI：10.1021/jm801627a

  日期：2009.3.26

  The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.