benzyl 5-amino-2-(benzyloxy)benzoate

• 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 5-amino-2-(benzyloxy)benzoate
• 英文别名: Benzyl 5-amino-2-(benzyloxy)benzoate；benzyl 5-amino-2-phenylmethoxybenzoate
• 化学式: C₂₁H₁₉NO₃
• 分子量: 333.387
• InChiKey: XICZFKDDJLPGJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  61.55
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  benzyl 5-amino-2-(benzyloxy)benzoate 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 benzyl 2-(benzyloxy)-5-((4-cyclohexylbenzyl)amino)benzoate
  参考文献：
  名称：

  Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma

  摘要：

  The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K-D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.

  DOI：

  10.1021/ml4003138
• 作为产物：
  描述：

  5-氨基水杨酸 、 溴甲苯 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 以75%的产率得到benzyl 5-amino-2-(benzyloxy)benzoate
  参考文献：
  名称：

  Potent Targeting of the STAT3 Protein in Brain Cancer Stem Cells: A Promising Route for Treating Glioblastoma

  摘要：

  The STAT3 gene is abnormally active in glioblastoma (GBM) and is a critically important mediator of tumor growth and therapeutic resistance in GBM. Thus, for poorly treated brain cancers such as gliomas, astrocytomas, and glioblastomas, which harbor constitutively activated STAT3, a STAT3-targeting therapeutic will be of significant importance. Herein, we report a most potent, small molecule, nonphosphorylated STAT3 inhibitor, 31 (SH-4-54) that strongly binds to STAT3 protein (K-D = 300 nM). Inhibitor 31 potently kills glioblastoma brain cancer stem cells (BTSCs) and effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets at low nM concentrations. Moreover, in vivo, 31 exhibited blood brain barrier permeability, potently controlled glioma tumor growth, and inhibited pSTAT3 in vivo. This work, for the first time, demonstrates the power of STAT3 inhibitors for the treatment of BTSCs and validates the therapeutic efficacy of a STAT3 inhibitor for GBM clinical application.

  DOI：

  10.1021/ml4003138

文献信息

• SALICYCLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
  申请人：The Governing Council of the University of Toronto

  公开号：US20150158894A1

  公开（公告）日：2015-06-11

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

  本发明涉及新型化合物、含有该化合物的组合物以及使用该化合物抑制STAT3和/或STAT5活性或治疗STAT3或STAT5依赖性癌症的方法；或其药学上可接受的盐、溶剂或前药。
• MONOCYCLIC PYRIDINE DERIVATIVE
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP2960238A1

  公开（公告）日：2015-12-30

  The present invention discloses a compound represented by the following formula (IA) or a pharmaceutically acceptable salt thereof: wherein n represents 0 to 2; A represents an arylene group or a heteroarylene group; G represents a single bond, an oxygen atom or -CH2-; E represents a nitrogen-containing non-aromatic heterocycle; R1 represents an alkoxy group, an alkoxy alkoxy group or the like; R2 represents a hydrogen atom, a halogen atom, a hydroxyl group, an alkyl group, a hydroxy alkyl group, a nitrogen-containing non-aromatic heterocyclic group or the like; R3 represents a hydrogen atom, an alkyl group, an alkoxy group or the like; and R4 represents a C1-6 alkyl group, with the proviso that when E represents an azetidine ring and R2 or R3 is present on a nitrogen atom on the azetidine ring, the R2 or R3 does not represent a hydrogen atom.

  本发明公开了由下式（IA）代表的化合物或其药学上可接受的盐： 其中 n 代表 0 至 2；A 代表芳基或杂芳基；G 代表单键、氧原子或-CH2-；E 代表含氮非芳香杂环；R1 代表烷氧基、烷氧基烷氧基或类似物；R2 代表氢原子、卤素原子、羟基、烷基、羟基烷基、含氮非芳香杂环基团或类似物；R3 代表氢原子、烷基、烷氧基或类似基团；以及 R4 代表 C1-6 烷基，但当 E 代表氮杂环丁烷环且 R2 或 R3 存在于氮杂环丁烷环上的氮原子上时，R2 或 R3 不代表氢原子。
• Salicylic acid derivatives, pharmaceutically acceptable salt thereof, composition thereof and method of use thereof
  申请人：The Governing Council of the University of Toronto

  公开号：US10377780B2

  公开（公告）日：2019-08-13

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.

  本发明涉及抑制 STAT3 和/或 STAT5 活性或使用上述化合物治疗 STAT3 或 STAT5 依赖性癌症的新型化合物、含有上述化合物的组合物和方法； 或其药学上可接受的盐、溶液或原药。
• NEW SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
  申请人：The Governing Council of the University of Toronto

  公开号：EP2854819A2

  公开（公告）日：2015-04-08
• SALICYLIC ACID DERIVATIVES, PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, COMPOSITION THEREOF AND METHOD OF USE THEREOF
  申请人：The Governing Council of the University of Toronto

  公开号：US20170267704A1

  公开（公告）日：2017-09-21

  The present invention relates to novel compounds, compositions containing same and methods for inhibiting STAT3 and/or STAT5 activity or for the treatment of a STAT3 or STAT5-dependent cancer using said compounds; or a pharmaceutically acceptable salt, solvate or prodrug thereof.