ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate | 1180676-75-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate
• 英文别名: (E)-ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate；ethyl (E)-5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate
• CAS: 1180676-75-8
• 化学式: C₁₉H₁₈BrFO₂
• 分子量: 377.253
• InChiKey: AHJRLNCNZIXXBK-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 以82%的产率得到PS 133
  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：

  3-(4-bromo-2-fluorophenyl)-1-phenylpropan-1-one 、 ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate 以(E)-ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate were obtained as colourless oils的产率得到ethyl 5-(4-bromo-2-fluorophenyl)-3-phenylpent-2-enoate
  参考文献：
  名称：

  Allosteric protein kinase modulators

  摘要：

  本发明提供了一种特定的小分子化合物，可以变构地调节AGC蛋白激酶和Aurora家族蛋白激酶的活性或调节它们之间的蛋白质相互作用，以及制备它们的方法、包含它们的制药组合物，以及它们用于制备治疗与AGC蛋白激酶或Aurora家族蛋白激酶异常活性相关的疾病的药物。

  公开号：

  US08912186B2