tetraethyl (((4-((4-methoxyphenyl)carbamoyl)pyridin-2-yl)amino)methylene)bis(phosphonate) | 1401111-02-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tetraethyl (((4-((4-methoxyphenyl)carbamoyl)pyridin-2-yl)amino)methylene)bis(phosphonate)
• CAS: 1401111-02-1
• 化学式: C₂₂H₃₃N₃O₈P₂
• 分子量: 529.467
• InChiKey: ITCCKEUFLCQBGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  35.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  134.31
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  tetraethyl (((4-((4-methoxyphenyl)carbamoyl)pyridin-2-yl)amino)methylene)bis(phosphonate) 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 120.0h， 以86%的产率得到[[[4-[(4-Methoxyphenyl)carbamoyl]pyridin-2-yl]amino]-phosphonomethyl]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：

  甲基异烟酸-N-氧化物 在 4-甲苯磺酸酐 、 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-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.5h， 生成 tetraethyl (((4-((4-methoxyphenyl)carbamoyl)pyridin-2-yl)amino)methylene)bis(phosphonate)
  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