2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyldiphosphonic acid | 1254582-53-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyldiphosphonic acid
• 英文别名: [1-fluoro-2-[5-(1H-indazol-5-yl)pyridin-3-yl]-1-phosphonoethyl]phosphonic acid
• CAS: 1254582-53-0
• 化学式: C₁₄H₁₄FN₃O₆P₂
• 分子量: 401.228
• InChiKey: MLYBZHHGRJJXOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  157
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tetraisopropyl (2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyl)bis(phosphonate) 在 盐酸 、 水 作用下， 生成 2-(5-(1H-indazol-5-yl)pyridin-3-yl)-1-fluoroethane-1,1-diyldiphosphonic acid
  参考文献：
  名称：

  Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase

  摘要：

  A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Preliminary SAR and structural evidence for the simultaneous binding of these inhibitors into the isopentenyl pyrophosphate (IPP) and the geranyl pyrophosphate (GPP) substrate sub-pockets of the enzyme are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.133

文献信息

• HETEROCYCLYL-PYRIDINYL-BASED BIPHOSPHONIC ACID, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
  申请人：Tsantrizos Youla S.

  公开号：US20130203702A1

  公开（公告）日：2013-08-08

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting human farnesyl pyrophosphate synthase or for the treatment or prevention of disease conditions using said compounds;

  本发明涉及新型化合物、含有该化合物的组合物以及使用该化合物抑制人类法尼醇焦磷酸合酶或治疗或预防疾病状况的方法；
• Design and Synthesis of Active Site Inhibitors of the Human Farnesyl Pyrophosphate Synthase: Apoptosis and Inhibition of ERK Phosphorylation in Multiple Myeloma Cells
  作者：Yih-Shyan Lin、Jaeok Park、Joris W. De Schutter、Xian Fang Huang、Albert M. Berghuis、Michael Sebag、Youla S. Tsantrizos

  DOI：10.1021/jm201657x

  日期：2012.4.12

  Human farnesyl pyrophosphate synthase (hFPPS) controls intracellular levels of FPP and post-translational prenylation of small GTPase proteins, which are essential for cell signaling and cell proliferation. Clinical investigations provide evidence that N-BP inhibitors of hFPPS are disease modifying agents that improve survival of multiple myeloma (MM) patients via mechanisms unrelated to their skeletal effects. A new series of N-BPs was designed that interact with a larger portion of the GPP subpocket, as compared to the current therapeutic drugs, and rigidify the (KRRK367)-K-364 tail of hFPPS in the closed conformation in the absence of IPP. An analogue of this series was used to demonstrate inhibition of the intended biological target, resulting in apoptosis and down-regulation of ERK phosphorylation in human MM cell lines.
• US8816082B2
  申请人：——

  公开号：US8816082B2

  公开（公告）日：2014-08-26
• US9290526B2
  申请人：——

  公开号：US9290526B2

  公开（公告）日：2016-03-22