2-((bis(diethoxyphosphoryl)methyl)amino)isonicotinic acid | 1401111-01-0

• 英文名称: 2-((bis(diethoxyphosphoryl)methyl)amino)isonicotinic acid
• CAS: 1401111-01-0
• 化学式: C₁₅H₂₆N₂O₈P₂
• 分子量: 424.328
• InChiKey: GADLNTCAMLTOFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  27.0
• 可旋转键数：
  13.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  133.28
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  2-((bis(diethoxyphosphoryl)methyl)amino)isonicotinic acid 在 三甲基溴硅烷 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 120.0h， 生成 [Phosphono-[[4-(propan-2-ylcarbamoyl)pyridin-2-yl]amino]methyl]phosphonic acid
  参考文献：
  名称：

  Design of potent bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase via targeted interactions with the active site ‘capping’ phenyls

  摘要：

  Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. N-BPs are also useful in combination chemotherapy for patients with breast, prostate and multiple myeloma cancers. A structure-based approach was employed in order to design inhibitors that exhibit higher lipophilicity and better occupancy for the GPP sub-pocket of hFPPS than the current therapeutic drugs. These novel analogs were designed to bind deeper into the GPP sub-pocket by displacing the side chains of the 'capping' residue Phe 113 and engaging in favorable p-interactions with the side chain of Phe112. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.019
• 作为产物：
  描述：

  异烟酸甲酯 在 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 甲苯 为溶剂， 反应 1.5h， 生成 2-((bis(diethoxyphosphoryl)methyl)amino)isonicotinic acid
  参考文献：
  名称：

  Design of potent bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase via targeted interactions with the active site ‘capping’ phenyls

  摘要：

  Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. N-BPs are also useful in combination chemotherapy for patients with breast, prostate and multiple myeloma cancers. A structure-based approach was employed in order to design inhibitors that exhibit higher lipophilicity and better occupancy for the GPP sub-pocket of hFPPS than the current therapeutic drugs. These novel analogs were designed to bind deeper into the GPP sub-pocket by displacing the side chains of the 'capping' residue Phe 113 and engaging in favorable p-interactions with the side chain of Phe112. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.019