2-((2,6-dichlorophenyl)(hydroxy)methyl)acrylonitrile | 1020666-62-9

• 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-((2,6-dichlorophenyl)(hydroxy)methyl)acrylonitrile
• 英文别名: 2-[(2,6-Dichlorophenyl)-hydroxymethyl]prop-2-enenitrile；2-[(2,6-dichlorophenyl)-hydroxymethyl]prop-2-enenitrile
• CAS: 1020666-62-9
• 化学式: C₁₀H₇Cl₂NO
• 分子量: 228.078
• InChiKey: VJFQLMKBSVUGNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-((2,6-dichlorophenyl)(hydroxy)methyl)acrylonitrile 、 乙酰氯 在 吡啶 作用下， 反应 3.0h， 生成 [2-Cyano-1-(2,6-dichlorophenyl)prop-2-enyl] acetate
  参考文献：
  名称：

  Synthesis of substituted 3-methylene-2-pyridones from Baylis–Hillman derivatives and its application for the generation of 2-pyridone substituted spiroisoxazolines

  摘要：

  The synthesis of substituted 3-methylene-2-pyridones via S(N)2 displacement reaction of nucleophiles bearing a keto group on the acetyl derivative of Baylis-Hillman adducts of acrylonitrile followed by TFA/H2SO4-mediated intramolecular cyclization is described. The utility of these pyridone derivatives for the synthesis of new spiroisoxazolines in highly regio- and stereo-selective fashion is also illustrated. The structure of the spiroisoxazolines has been secured via X-ray crystallographic analysis. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2008.01.074
• 作为产物：
  描述：

  2,6-二氯苯甲醛 、 丙烯腈 在 三乙烯二胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 66.0h， 以21%的产率得到2-((2,6-dichlorophenyl)(hydroxy)methyl)acrylonitrile
  参考文献：
  名称：

  Electrophilic Warhead-Based Design of Compounds Preventing NLRP3 Inflammasome-Dependent Pyroptosis

  摘要：

  Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we describe the synthesis and chemical tuning of alpha,beta-unsaturated electrophilic warheads toward the development of antipyroptotic compounds. Their pharmacological evaluation and structure-activity relationships are also described. Compound 9 was selected as a model of this series, and it proved to be a reactive Michael acceptor, irreversibly trapping thiol nucleophiles, which prevented both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner. Moreover, 9 and other structurally related compounds, inhibited caspase-1 and NLRP3 ATPase activities. Our findings can contribute to the development of covalent, multitarget antipyroptotic compounds targeting molecular components of the NLRP3 inflammasome regulatory pathway.

  DOI：

  10.1021/jm501072b

文献信息

• Synthesis of substituted 3-methylene-2-pyridones from Baylis–Hillman derivatives and its application for the generation of 2-pyridone substituted spiroisoxazolines
  作者：Virender Singh、Gaya P. Yadav、Prakas R. Maulik、Sanjay Batra

  DOI：10.1016/j.tet.2008.01.074

  日期：2008.3

  The synthesis of substituted 3-methylene-2-pyridones via S(N)2 displacement reaction of nucleophiles bearing a keto group on the acetyl derivative of Baylis-Hillman adducts of acrylonitrile followed by TFA/H2SO4-mediated intramolecular cyclization is described. The utility of these pyridone derivatives for the synthesis of new spiroisoxazolines in highly regio- and stereo-selective fashion is also illustrated. The structure of the spiroisoxazolines has been secured via X-ray crystallographic analysis. (C) 2008 Elsevier Ltd. All rights reserved.
• Electrophilic Warhead-Based Design of Compounds Preventing NLRP3 Inflammasome-Dependent Pyroptosis
  作者：Mattia Cocco、Davide Garella、Antonella Di Stilo、Emily Borretto、Livio Stevanato、Marta Giorgis、Elisabetta Marini、Roberto Fantozzi、Gianluca Miglio、Massimo Bertinaria

  DOI：10.1021/jm501072b

  日期：2014.12.26

  Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we describe the synthesis and chemical tuning of alpha,beta-unsaturated electrophilic warheads toward the development of antipyroptotic compounds. Their pharmacological evaluation and structure-activity relationships are also described. Compound 9 was selected as a model of this series, and it proved to be a reactive Michael acceptor, irreversibly trapping thiol nucleophiles, which prevented both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner. Moreover, 9 and other structurally related compounds, inhibited caspase-1 and NLRP3 ATPase activities. Our findings can contribute to the development of covalent, multitarget antipyroptotic compounds targeting molecular components of the NLRP3 inflammasome regulatory pathway.