2-[(pyridin-3-yl)ethyl] diphosphate | 1227924-70-0

• 分子结构分类: 有机化合物 - 有机氧化合物 - 有机含氧阴离子化合物
• 英文名称: 2-[(pyridin-3-yl)ethyl] diphosphate
• 英文别名: pyridin-3-yl-ethyl-diphosphate；phosphono 2-pyridin-3-ylethyl hydrogen phosphate
• CAS: 1227924-70-0
• 化学式: C₇H₁₁NO₇P₂
• 分子量: 283.114
• InChiKey: SMIWJXJRPPYIHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-(2-溴 乙基)吡啶 在 tris(tetra-n-butylammonium) hydrogen pyrophosphate 作用下， 以 乙腈 为溶剂， 以25%的产率得到2-[(pyridin-3-yl)ethyl] diphosphate
  参考文献：
  名称：

  Inhibition of the Fe₄S₄-Cluster-Containing Protein IspH (LytB): Electron Paramagnetic Resonance, Metallacycles, and Mechanisms

  摘要：

  We report the inhibition of the Aquifex aeolicus IspH enzyme (LytB, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, EC 1.17.1.2) by a series of diphosphates and bisphosphonates. The most active species was an alkryl diphosphate having IC50 = 0.45 mu M (K-i approximate to 60 nM), which generated a very large change in the 9 GHz EPR spectrum of the reduced protein. On the basis of previous work on organometallic complexes, together with computational docking and quantum chemical calculations, we propose a model for alkyne inhibition involving pi (or pi/sigma) "metallacycle" complex formation with the unique fourth Fe in the Fe4S4 cluster. Aromatic species had less activity, and for these we propose an inhibition model based on an electrostatic interaction with the active site E126. Overall, the results are of broad general interest since they not only represent the first potent IspH inhibitors but also suggest a conceptually new approach to inhibiting other Fe4S4-cluster-containing proteins that are of interest as drug and herbicide targets.

  DOI：

  10.1021/ja909664j

文献信息

• [EN] ENZYME INHIBITING COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS INHIBITEURS D'ENZYME
  申请人：UNIV ILLINOIS

  公开号：WO2011044505A3

  公开（公告）日：2011-08-18
• Inhibition of the Fe₄S₄-Cluster-Containing Protein IspH (LytB): Electron Paramagnetic Resonance, Metallacycles, and Mechanisms
  作者：Ke Wang、Weixue Wang、Joo-Hwan No、Yonghui Zhang、Yong Zhang、Eric Oldfield

  DOI：10.1021/ja909664j

  日期：2010.5.19

  We report the inhibition of the Aquifex aeolicus IspH enzyme (LytB, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, EC 1.17.1.2) by a series of diphosphates and bisphosphonates. The most active species was an alkryl diphosphate having IC50 = 0.45 mu M (K-i approximate to 60 nM), which generated a very large change in the 9 GHz EPR spectrum of the reduced protein. On the basis of previous work on organometallic complexes, together with computational docking and quantum chemical calculations, we propose a model for alkyne inhibition involving pi (or pi/sigma) "metallacycle" complex formation with the unique fourth Fe in the Fe4S4 cluster. Aromatic species had less activity, and for these we propose an inhibition model based on an electrostatic interaction with the active site E126. Overall, the results are of broad general interest since they not only represent the first potent IspH inhibitors but also suggest a conceptually new approach to inhibiting other Fe4S4-cluster-containing proteins that are of interest as drug and herbicide targets.