ethyl (E)-4-(4-chlorophenoxy)-3-phenylbut-2-enoate | 1180676-96-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl (E)-4-(4-chlorophenoxy)-3-phenylbut-2-enoate
• 英文别名: (E)-ethyl 4-(4-chlorophenylthio)-3-phenylbut-2-enoate；ethyl (E)-4-(4-chlorophenyl)sulfanyl-3-phenylbut-2-enoate
• CAS: 1180676-96-3
• 化学式: C₁₈H₁₇ClO₂S
• 分子量: 332.851
• InChiKey: DKYGYCQRWDBPIF-QINSGFPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (E)-4-(4-chlorophenoxy)-3-phenylbut-2-enoate 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以60%的产率得到(E)-4-(4-chlorophenylthio)-3-phenylbut-2-enoic acid
  参考文献：
  名称：

  3,5-Diphenylpent-2-enoic Acids as Allosteric Activators of the Protein Kinase PDK1: Structure−Activity Relationships and Thermodynamic Characterization of Binding as Paradigms for PIF-Binding Pocket-Targeting Compounds†PDB code of 2Z with PDK1: 3HRF.

  摘要：

  The modulation of protein kinase activities by low molecular weight compounds is a major goal of current pharmaceutical developments. In this line, important efforts are directed to the development of drugs targeting the conserved ATP binding site. However, there is very little experience on targeting allosteric, regulatory sites, different from the ATP binding site, in protein kinases. Here we describe the synthesis, cell-free activation potency, and calorimetric binding analysis of 3,5-diphenylpent-2-enoic acids and derivatives as allosteric modulators of the phosphoinositide-dependent kinase-1 (PDK 1) catalytic activity. Our SAR results combined with thermodynamic binding analyses revealed both favorable binding enthalpy and entropy and confirmed the PIF-binding pocket of PDK I as a druggable site. In conclusion, we defined the minimal structural requirements for compounds to bind to the PIF-binding pocket and to act as allosteric modulators and identified two new lead structures (12Z and 13Z) with predominating binding enthalpy.

  DOI：

  10.1021/jm9001499
• 作为产物：
  描述：

  磷酰基乙酸三乙酯 、 2-(4-氯苯基)硫烷基-1-苯基乙酮 在 sodium hydride 作用下， 以 乙二醇二甲醚 、 mineral oil 为溶剂， 反应 5.0h， 以63%的产率得到ethyl (E)-4-(4-chlorophenoxy)-3-phenylbut-2-enoate
  参考文献：
  名称：

  3,5-Diphenylpent-2-enoic Acids as Allosteric Activators of the Protein Kinase PDK1: Structure−Activity Relationships and Thermodynamic Characterization of Binding as Paradigms for PIF-Binding Pocket-Targeting Compounds†PDB code of 2Z with PDK1: 3HRF.

  摘要：

  The modulation of protein kinase activities by low molecular weight compounds is a major goal of current pharmaceutical developments. In this line, important efforts are directed to the development of drugs targeting the conserved ATP binding site. However, there is very little experience on targeting allosteric, regulatory sites, different from the ATP binding site, in protein kinases. Here we describe the synthesis, cell-free activation potency, and calorimetric binding analysis of 3,5-diphenylpent-2-enoic acids and derivatives as allosteric modulators of the phosphoinositide-dependent kinase-1 (PDK 1) catalytic activity. Our SAR results combined with thermodynamic binding analyses revealed both favorable binding enthalpy and entropy and confirmed the PIF-binding pocket of PDK I as a druggable site. In conclusion, we defined the minimal structural requirements for compounds to bind to the PIF-binding pocket and to act as allosteric modulators and identified two new lead structures (12Z and 13Z) with predominating binding enthalpy.

  DOI：

  10.1021/jm9001499

文献信息

• 3,5-Diphenylpent-2-enoic Acids as Allosteric Activators of the Protein Kinase PDK1: Structure−Activity Relationships and Thermodynamic Characterization of Binding as Paradigms for PIF-Binding Pocket-Targeting Compounds†PDB code of <b>2Z</b> with PDK1: 3HRF.
  作者：Adriana Stroba、Francis Schaeffer、Valerie Hindie、Laura Lopez-Garcia、Iris Adrian、Wolfgang Fröhner、Rolf W. Hartmann、Ricardo M. Biondi、Matthias Engel

  DOI：10.1021/jm9001499

  日期：2009.8.13

  The modulation of protein kinase activities by low molecular weight compounds is a major goal of current pharmaceutical developments. In this line, important efforts are directed to the development of drugs targeting the conserved ATP binding site. However, there is very little experience on targeting allosteric, regulatory sites, different from the ATP binding site, in protein kinases. Here we describe the synthesis, cell-free activation potency, and calorimetric binding analysis of 3,5-diphenylpent-2-enoic acids and derivatives as allosteric modulators of the phosphoinositide-dependent kinase-1 (PDK 1) catalytic activity. Our SAR results combined with thermodynamic binding analyses revealed both favorable binding enthalpy and entropy and confirmed the PIF-binding pocket of PDK I as a druggable site. In conclusion, we defined the minimal structural requirements for compounds to bind to the PIF-binding pocket and to act as allosteric modulators and identified two new lead structures (12Z and 13Z) with predominating binding enthalpy.