2-(4-Nitrophenyl)sulfonyloxirane | 1404061-00-2

• 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: 2-(4-Nitrophenyl)sulfonyloxirane
• CAS: 1404061-00-2
• 化学式: C₈H₇NO₅S
• 分子量: 229.213
• InChiKey: UXKKHHBDGZYDQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-硝基苯基乙烯基砜 在 叔丁基过氧化氢 、 正丁基锂 作用下， 以 四氢呋喃 、 癸烷 、 正己烷 为溶剂， 以55%的产率得到2-(4-Nitrophenyl)sulfonyloxirane
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of 2-(arylsulfonyl)oxiranes as Cell-permeable Covalent Inhibitors of Protein Tyrosine Phosphatases

  摘要：

  A structure‐based design approach has been applied to develop 2‐(arylsulfonyl)oxiranes as potential covalent inhibitors of protein tyrosine phosphatases. A detailed kinetic analysis of inactivation by these covalent inhibitors reveals that this class of compounds inhibits a panel of protein tyrosine phosphatases in a time‐ and dose‐dependent manner, consistent with the covalent modification of the enzyme active site. An inactivation experiment in the presence of sodium arsenate, a known competitive inhibitor of protein tyrosine phosphatase, indicated that these inhibitors were active site bound. This finding is consistent with the mass spectrometric analysis of the covalently modified protein tyrosine phosphatase enzyme. Additional experiments indicated that these compounds remained inert toward other classes of arylphosphate‐hydrolyzing enzymes, and alkaline and acid phosphatases. Cell‐based experiments with human A549 lung cancer cell lines indicated that 2‐(phenylsulfonyl)oxirane (1) caused an increase in intracellular pTyr levels in a dose‐dependent manner thereby suggesting its cell‐permeable nature. Taken together, the newly identified 2‐(arylsulfonyl)oxiranyl moiety could serve as a novel chemotype for the development of activity‐based probes and therapeutic agents against protein tyrosine phosphatase superfamily of enzymes.

  DOI：

  10.1111/j.1747-0285.2012.01437.x

文献信息

• Design, Synthesis, and Evaluation of 2-(arylsulfonyl)oxiranes as Cell-permeable Covalent Inhibitors of Protein Tyrosine Phosphatases
  作者：Dibyendu Dana、Tirtha K. Das、Ish Kumar、Anibal R. Davalos、Kevin J. Mark、Daryl Ramai、Emmanuel J. Chang、Tanaji T. Talele、Sanjai Kumar

  DOI：10.1111/j.1747-0285.2012.01437.x

  日期：2012.10

  A structure‐based design approach has been applied to develop 2‐(arylsulfonyl)oxiranes as potential covalent inhibitors of protein tyrosine phosphatases. A detailed kinetic analysis of inactivation by these covalent inhibitors reveals that this class of compounds inhibits a panel of protein tyrosine phosphatases in a time‐ and dose‐dependent manner, consistent with the covalent modification of the enzyme active site. An inactivation experiment in the presence of sodium arsenate, a known competitive inhibitor of protein tyrosine phosphatase, indicated that these inhibitors were active site bound. This finding is consistent with the mass spectrometric analysis of the covalently modified protein tyrosine phosphatase enzyme. Additional experiments indicated that these compounds remained inert toward other classes of arylphosphate‐hydrolyzing enzymes, and alkaline and acid phosphatases. Cell‐based experiments with human A549 lung cancer cell lines indicated that 2‐(phenylsulfonyl)oxirane (1) caused an increase in intracellular pTyr levels in a dose‐dependent manner thereby suggesting its cell‐permeable nature. Taken together, the newly identified 2‐(arylsulfonyl)oxiranyl moiety could serve as a novel chemotype for the development of activity‐based probes and therapeutic agents against protein tyrosine phosphatase superfamily of enzymes.