3-Nitro-4-hydroxy-benzyloxyamin | 50837-36-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3-Nitro-4-hydroxy-benzyloxyamin
• 英文别名: 4-[(Aminooxy)methyl]-2-nitrophenol；4-(aminooxymethyl)-2-nitrophenol
• CAS: 50837-36-0
• 化学式: C₇H₈N₂O₄
• 分子量: 184.152
• InChiKey: PITNDATVERTKEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Nitro-4-hydroxy-benzyloxyamin 在 四氯化碳 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 4-((aminooxy)methyl)-2-nitrophenyl dihydrogen phosphate
  参考文献：
  名称：

  Utilization of Nitrophenylphosphates and Oxime-Based Ligation for the Development of Nanomolar Affinity Inhibitors of the Yersinia pestis Outer Protein H (YopH) Phosphatase

  摘要：

  Our current study reports the first K(M) optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K(M) = 80 mu M) was converted from a subs trate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid, and by attachment of an aminooxy handle for further structural optimization by mime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequenly employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC(50) = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition Of intracellular Y pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.

  DOI：

  10.1021/jm200022g

文献信息

• Utilization of Nitrophenylphosphates and Oxime-Based Ligation for the Development of Nanomolar Affinity Inhibitors of the <i>Yersinia pestis</i> Outer Protein H (YopH) Phosphatase
  作者：Medhanit Bahta、George T. Lountos、Beverly Dyas、Sung-Eun Kim、Robert G. Ulrich、David S. Waugh、Terrence R. Burke

  DOI：10.1021/jm200022g

  日期：2011.4.28

  Our current study reports the first K(M) optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K(M) = 80 mu M) was converted from a subs trate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid, and by attachment of an aminooxy handle for further structural optimization by mime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequenly employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC(50) = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition Of intracellular Y pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.