benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2-methylbenzyl)phenylsulfonamido)acetamido)benzoate | 1455006-18-4

• 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: benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2-methylbenzyl)phenylsulfonamido)acetamido)benzoate
• CAS: 1455006-18-4
• 化学式: C₅₀H₄₅F₅N₂O₆S
• 分子量: 896.975
• InChiKey: QQDPFVBKXVRXPY-UHFFFAOYSA-N

物化性质

• 沸点：
  931.1±75.0 °C(predicted)
• 密度：
  1.330±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  11.1
• 重原子数：
  64.0
• 可旋转键数：
  16.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93.22
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2-methylbenzyl)phenylsulfonamido)acetamido)benzoate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 以83%的产率得到4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2-methylbenzyl)phenylsulfonamido)acetamido)-2-hydroxybenzoic acid
  参考文献：
  名称：

  Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma

  摘要：

  The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3-4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity in vitro. These compounds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations.

  DOI：

  10.1021/jm3017255
• 作为产物：
  描述：

  benzyl 4-amino-2-(benzyloxy)benzoate 在 哌啶 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 、 三苯基二氯化膦 作用下， 以 甲醇 、 氘代氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.75h， 生成 benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-(2-methylbenzyl)phenylsulfonamido)acetamido)benzoate
  参考文献：
  名称：

  Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma

  摘要：

  The signal transducer and activator of transcription (STAT) proteins represent a family of cytoplasmic transcription factors that regulate a pleiotropic range of biological processes. In particular, Stat3 protein has attracted attention as it regulates the expression of genes involved in a variety of malignant processes, including proliferation, survival, migration, and drug resistance. Multiple myeloma (MM) is an incurable hematologic malignancy that often exhibits abnormally high levels of Stat3 activity. Although current treatment strategies can improve the clinical management of MM, it remains uniformly incurable with a dismal median survival time post-treatment of 3-4 years. Thus, novel targeted therapeutics are critically needed to improve MM patient outcomes. We herein report the development of a series of small molecule Stat3 inhibitors with potent anti-MM activity in vitro. These compounds showed high-affinity binding to Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced apoptosis in MM cell lines at low micromolar concentrations.

  DOI：

  10.1021/jm3017255