3-甲氧基-4-((4-((3-氧代-2,3-二氢-1H-茚-4-基)氧基)-5-(三氟甲基)嘧啶-2-基)氨基)苯甲酸 | 1227948-58-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3-甲氧基-4-((4-((3-氧代-2,3-二氢-1H-茚-4-基)氧基)-5-(三氟甲基)嘧啶-2-基)氨基)苯甲酸
• 英文名称: 3-methoxy-4-({4-[(3-oxo-2,3-dihydro-1H-inden-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoic acid
• 英文别名: 3-Methoxy-4-((4-((3-oxo-2,3-dihydro-1H-inden-4-yl)oxy)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoic acid；3-methoxy-4-[[4-[(3-oxo-1,2-dihydroinden-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzoic acid
• CAS: 1227948-58-4
• 化学式: C₂₂H₁₆F₃N₃O₅
• 分子量: 459.381
• InChiKey: OTTSPUXLGPFKPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-氨基-1-甲基哌啶 、 3-甲氧基-4-((4-((3-氧代-2,3-二氢-1H-茚-4-基)氧基)-5-(三氟甲基)嘧啶-2-基)氨基)苯甲酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 以75%的产率得到3-methoxy-N-(1-methylpiperidin-4-yl)-4-({4-[(3-oxo-2,3-dihydro-1H-inden-4-yl)oxy]-5-(trifluoromethyl)pyrimidin-2-yl}amino)-benzamide
  参考文献：
  名称：

  Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

  摘要：

  Focal adhesion tyrosine kinase (PTK2) is often overexpressed in human hepatocellular carcinoma (HCC), and several reports have linked PTK2 depletion and/or pharmacological inhibition to reduced tumorigenicity. However, the clinical relevance of targeting PTK2 still remains to be proven. Here, we present two highly selective and functional PTK2 proteolysis-targeting chimeras utilizing von Hippel-Lindau and cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 (cereblon-based) degrades PTK2 with a median DC50 of 30 nM to >80% across a panel of 11 HCC cell lines. Despite effective PTK2 degradation, these compounds did not phenocopy the reported antiproliferative effects of PTK2 depletion in any of the cell lines tested. By disclosing these compounds, we hope to provide valuable tools for the study of PTK2 degradation across different biological systems.

  DOI：

  10.1021/acs.jmedchem.8b01826
• 作为产物：
  描述：

  7-羟基-1-茚酮 、 4-{[4-chloro-5-(trifluoromethyl)pyrimidin-2-yl]amino}-3-methoxybenzoic acid 在 caesium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以78%的产率得到3-甲氧基-4-((4-((3-氧代-2,3-二氢-1H-茚-4-基)氧基)-5-(三氟甲基)嘧啶-2-基)氨基)苯甲酸
  参考文献：
  名称：

  Highly Selective PTK2 Proteolysis Targeting Chimeras to Probe Focal Adhesion Kinase Scaffolding Functions

  摘要：

  Focal adhesion tyrosine kinase (PTK2) is often overexpressed in human hepatocellular carcinoma (HCC), and several reports have linked PTK2 depletion and/or pharmacological inhibition to reduced tumorigenicity. However, the clinical relevance of targeting PTK2 still remains to be proven. Here, we present two highly selective and functional PTK2 proteolysis-targeting chimeras utilizing von Hippel-Lindau and cereblon ligands to hijack E3 ligases for PTK2 degradation. BI-3663 (cereblon-based) degrades PTK2 with a median DC50 of 30 nM to >80% across a panel of 11 HCC cell lines. Despite effective PTK2 degradation, these compounds did not phenocopy the reported antiproliferative effects of PTK2 depletion in any of the cell lines tested. By disclosing these compounds, we hope to provide valuable tools for the study of PTK2 degradation across different biological systems.

  DOI：

  10.1021/acs.jmedchem.8b01826

文献信息

• SUBSTITUTED PYRIMIDINES FOR THE TREATMENT OF DISEASES SUCH AS CANCER
  申请人：Stadtmueller Heinz

  公开号：US20110288071A1

  公开（公告）日：2011-11-24

  The present invention encompasses compounds of general formula (1) wherein A, B, X, R 1 to R 3 are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a medicament having the above-mentioned properties.

  本发明涵盖通式（1）中A，B，X，R1至R3如权利要求1所定义的化合物，适用于治疗由过度或异常细胞增殖特征的疾病，并用于制备具有上述特性的药物。
• NEW COMPOUNDS
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20150376141A1

  公开（公告）日：2015-12-31

  The present invention encompasses compounds of general formula (1) wherein A, B, X, R 1 to R 3 are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a medicament having the above-mentioned properties.

  本发明涵盖了通式（1）中定义的化合物，其中A，B，X，R1至R3的定义如权利要求书中所述，适用于治疗由过度或异常细胞增殖所特征的疾病，并且它们的用途用于制备具有上述特性的药物。
• US8846689B2
  申请人：——

  公开号：US8846689B2

  公开（公告）日：2014-09-30
• US9676762B2
  申请人：——

  公开号：US9676762B2

  公开（公告）日：2017-06-13