benzyl 4-(2-amino-N-(4-cyclohexylbenzyl)acetamido)-2-(benzyloxy)benzoate | 1455006-13-9

• 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: benzyl 4-(2-amino-N-(4-cyclohexylbenzyl)acetamido)-2-(benzyloxy)benzoate
• 英文别名: Benzyl 4-[(2-aminoacetyl)-[(4-cyclohexylphenyl)methyl]amino]-2-phenylmethoxybenzoate；benzyl 4-[(2-aminoacetyl)-[(4-cyclohexylphenyl)methyl]amino]-2-phenylmethoxybenzoate
• CAS: 1455006-13-9
• 化学式: C₃₆H₃₈N₂O₄
• 分子量: 562.709
• InChiKey: PMYSCEJKOYGXIT-UHFFFAOYSA-N

物化性质

• 沸点：
  741.8±60.0 °C(predicted)
• 密度：
  1.197±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 4-(2-amino-N-(4-cyclohexylbenzyl)acetamido)-2-(benzyloxy)benzoate 在 potassium carbonate 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 benzyl 2-(benzyloxy)-4-(N-(4-cyclohexylbenzyl)-2-(2,3,4,5,6-pentafluoro-N-methylphenylsulfonamido)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
• 作为产物：
  描述：

  benzyl 4-amino-2-(benzyloxy)benzoate 在 哌啶 、 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 为溶剂， 反应 3.75h， 生成 benzyl 4-(2-amino-N-(4-cyclohexylbenzyl)acetamido)-2-(benzyloxy)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

文献信息

• Inhibiting Aberrant Signal Transducer and Activator of Transcription Protein Activation with Tetrapodal, Small Molecule Src Homology 2 Domain Binders: Promising Agents against Multiple Myeloma
  作者：Brent D. G. Page、Danielle C. Croucher、Zhi Hua Li、Sina Haftchenary、Victor H. Jimenez-Zepeda、Jennifer Atkinson、Paul A. Spagnuolo、Yoong Lim Wong、Robert Colaguori、Andrew M. Lewis、Aaron D. Schimmer、Suzanne Trudel、Patrick T. Gunning

  DOI：10.1021/jm3017255

  日期：2013.9.26

  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.