(2R,3R,4S,5R)-2-(6-amino-8-((3,4-dichlorobenzyl)amino)-9Hpurin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol | 1134156-17-4

• 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: (2R,3R,4S,5R)-2-(6-amino-8-((3,4-dichlorobenzyl)amino)-9Hpurin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
• 英文别名: (2R,3R,4S,5R)-2-[6-amino-8-(3,4-dichlorobenzylamino)purin-9-yl]-5-hydroxymethyl-tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-[6-amino-8-[(3,4-dichlorophenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 1134156-17-4
• 化学式: C₁₇H₁₈Cl₂N₆O₄
• 分子量: 441.274
• InChiKey: VBJKVZXRYLCYGQ-XNIJJKJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  152
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,4-二氯苄胺 、 8-溴膘苷 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以73%的产率得到(2R,3R,4S,5R)-2-(6-amino-8-((3,4-dichlorobenzyl)amino)-9Hpurin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  利用蛋白质构象变化优化 HSP70 的腺苷衍生抑制剂

  摘要：

  HSP70 是一种分子伴侣，是热休克反应的关键组成部分。由于其在肿瘤学中的重要性，这种蛋白质已成为药物发现的热门目标，但这些努力尚未取得成功。该研究表明，腺苷衍生的 HSP70 抑制剂可能以一种新的作用机制与蛋白质结合，通过分子内盐桥的去溶剂化来稳定化，从而诱导蛋白质的构象变化，从而产生高亲和力配体。我们还证明，通过这种机制的应用，可以以合理的方式优化腺苷衍生的 HSP70 抑制剂。

  DOI：

  10.1021/acs.jmedchem.5b02001

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.
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70
  作者：Matthew D. Cheeseman、Isaac M. Westwood、Olivier Barbeau、Martin Rowlands、Sarah Dobson、Alan M. Jones、Fiona Jeganathan、Rosemary Burke、Nadia Kadi、Paul Workman、Ian Collins、Rob L. M. van Montfort、Keith Jones

  DOI：10.1021/acs.jmedchem.5b02001

  日期：2016.5.26

  importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity

  HSP70 是一种分子伴侣，是热休克反应的关键组成部分。由于其在肿瘤学中的重要性，这种蛋白质已成为药物发现的热门目标，但这些努力尚未取得成功。该研究表明，腺苷衍生的 HSP70 抑制剂可能以一种新的作用机制与蛋白质结合，通过分子内盐桥的去溶剂化来稳定化，从而诱导蛋白质的构象变化，从而产生高亲和力配体。我们还证明，通过这种机制的应用，可以以合理的方式优化腺苷衍生的 HSP70 抑制剂。