diethyl 2-(3-oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonate | 1221962-87-3

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: diethyl 2-(3-oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonate
• 英文别名: diethyl 2-[3-oxo-1-phenylpropyl-3-(4-trifluoromethylphenyl)]malonate；Diethyl 2-[3-oxo-1-phenyl-3-[4-(trifluoromethyl)phenyl]propyl]propanedioate
• CAS: 1221962-87-3
• 化学式: C₂₃H₂₃F₃O₅
• 分子量: 436.428
• InChiKey: MSYZZISLPYXNMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl 2-(3-oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonate 在 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 bis(acetoxymethyl)2-(3-oxo-1-phenyl-3-(4 (trifluoromethyl)phenyl)propyl)-malonate
  参考文献：
  名称：

  2-(3-Oxo-1,3-diphenylpropyl)malonic Acids as Potent Allosteric Ligands of the PIF Pocket of Phosphoinositide-Dependent Kinase-1: Development and Prodrug Concept

  摘要：

  The protein kinase C-related kinase 2 (PRK2)interacting fragment (PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric modulators. In the present work, We describe the design, synthesis, and structure-activity relationship of a series of 2-(3-oxo-1,3- diphenylprapyl)malonic acids as potent allosteric activators binding, to the PIF pocket: Some congeners displayed AC(50) values for PDK1 activation in the submicromolar range. The potency of the best compounds to stabilize PDK1 in a thermal stability shift assay was in the same order Of magnitude as that of the PIF pocket binding peptide PIFtide, suggesting comparable binding affinities to the pm pocket, The crystal structure of PDK1 in complex with compound 4h revealed that additional ionic interactions are mainly responsible for the increased potency compared to the monocarboxylate analogues. Notably, several compounds displayed high selectivity for PDK1 Employing a prodrug strategy, we were able to corrroborate the novel mechanism of action in cells.

  DOI：

  10.1021/jm3010477
• 作为产物：
  描述：

  4'-三氟甲基苯乙酮 在 magnesium oxide 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 3.0h， 生成 diethyl 2-(3-oxo-1-phenyl-3-(4-(trifluoromethyl)phenyl)propyl)malonate
  参考文献：
  名称：

  2-(3-Oxo-1,3-diphenylpropyl)malonic Acids as Potent Allosteric Ligands of the PIF Pocket of Phosphoinositide-Dependent Kinase-1: Development and Prodrug Concept

  摘要：

  The protein kinase C-related kinase 2 (PRK2)interacting fragment (PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric modulators. In the present work, We describe the design, synthesis, and structure-activity relationship of a series of 2-(3-oxo-1,3- diphenylprapyl)malonic acids as potent allosteric activators binding, to the PIF pocket: Some congeners displayed AC(50) values for PDK1 activation in the submicromolar range. The potency of the best compounds to stabilize PDK1 in a thermal stability shift assay was in the same order Of magnitude as that of the PIF pocket binding peptide PIFtide, suggesting comparable binding affinities to the pm pocket, The crystal structure of PDK1 in complex with compound 4h revealed that additional ionic interactions are mainly responsible for the increased potency compared to the monocarboxylate analogues. Notably, several compounds displayed high selectivity for PDK1 Employing a prodrug strategy, we were able to corrroborate the novel mechanism of action in cells.

  DOI：

  10.1021/jm3010477