| 1365538-66-4

• CAS: 1365538-66-4
• 化学式: C₂₁H₃₂N₂O₇P₂
• 分子量: 486.442
• InChiKey: QMRYQEBRSRZQLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.98
• 重原子数：
  32.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  105.21
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  在 甲醇 作用下， 以 二氯甲烷 为溶剂， 生成 [[[4-(2-Methoxyphenyl)pyridin-2-yl]amino]-phosphonomethyl]phosphonic acid
  参考文献：
  名称：

  Design and Synthesis of Active Site Inhibitors of the Human Farnesyl Pyrophosphate Synthase: Apoptosis and Inhibition of ERK Phosphorylation in Multiple Myeloma Cells

  摘要：

  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.

  DOI：

  10.1021/jm201657x