(R)-1-(2-amino-4-(trifluoromethyl)phenyl)-N,N-dimethylpyrrolidin-3-amine | 870220-88-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (R)-1-(2-amino-4-(trifluoromethyl)phenyl)-N,N-dimethylpyrrolidin-3-amine
• 英文别名: (R)-1-(2-amino-4-trifluoromethyl-phenyl)-N,N-dimethylpyrrolidin-3-amine；(3R)-1-[2-amino-4-(trifluoromethyl)phenyl]-N,N-dimethylpyrrolidin-3-amine
• CAS: 870220-88-5
• 化学式: C₁₃H₁₈F₃N₃
• 分子量: 273.301
• InChiKey: WBDBBVWLLPEZEM-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-1-(2-amino-4-(trifluoromethyl)phenyl)-N,N-dimethylpyrrolidin-3-amine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 3.0h， 生成 (R)-5-(2-(2-aminopyrimidin-5-yl)ethynyl)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-5-(trifluoromethyl)phenyl)-2-fluorobenzamide
  参考文献：
  名称：

  Alkynylpyrimidine Amide Derivatives as Potent, Selective, and Orally Active Inhibitors of Tie-2 Kinase

  摘要：

  The recognition that aberrant angiogenesis contributes to the pathology of inflammatory diseases, cancer, and myocardial ischemia has generated considerable interest in the molecular mechanisms that regulate blood vessel growth. The receptor tyrosine kinase Tie-2 is expressed primarily by vascular endothelial cells and is critical for embryonic vasculogenesis. Interference with the Tie-2 pathway by diverse blocking agents such as soluble Tie-2 receptors, anti-Tie-2 intrabodies, anti-Ang-2 antibodies, and peptide-F-c conjugates has been shown to suppress tumor growth in xenograft studies. An alternative strategy for interfering with the Tie-2 signaling pathway involves direct inhibition of the kinase functions of the Tie-2 receptor. Herein we describe the development of alkynylpyrimidine amide derivatives as potent, selective, and orally available ATP-competitive inhibitors of Tie-2 autophosphorylation.

  DOI：

  10.1021/jm061112p
• 作为产物：
  描述：

  4-氟-3-硝基三氟甲苯 在 palladium on activated charcoal 氢气 、 碳酸氢钠 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 14.0h， 生成 (R)-1-(2-amino-4-(trifluoromethyl)phenyl)-N,N-dimethylpyrrolidin-3-amine
  参考文献：
  名称：

  Alkynylpyrimidine Amide Derivatives as Potent, Selective, and Orally Active Inhibitors of Tie-2 Kinase

  摘要：

  The recognition that aberrant angiogenesis contributes to the pathology of inflammatory diseases, cancer, and myocardial ischemia has generated considerable interest in the molecular mechanisms that regulate blood vessel growth. The receptor tyrosine kinase Tie-2 is expressed primarily by vascular endothelial cells and is critical for embryonic vasculogenesis. Interference with the Tie-2 pathway by diverse blocking agents such as soluble Tie-2 receptors, anti-Tie-2 intrabodies, anti-Ang-2 antibodies, and peptide-F-c conjugates has been shown to suppress tumor growth in xenograft studies. An alternative strategy for interfering with the Tie-2 signaling pathway involves direct inhibition of the kinase functions of the Tie-2 receptor. Herein we describe the development of alkynylpyrimidine amide derivatives as potent, selective, and orally available ATP-competitive inhibitors of Tie-2 autophosphorylation.

  DOI：

  10.1021/jm061112p

文献信息

• Aryl nitrogen-containing bicyclic compounds and methods of use
  申请人：Patel F. Vinod

  公开号：US20070054916A1

  公开（公告）日：2007-03-08

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , B, R 1 , R 2 , R 3 and R 4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  这项发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。这些化合物具有一般的化学式I，其中A1、A2、A3、B、R1、R2、R3和R4在此有定义。因此，该发明还涉及包括该发明的化合物的药物组合物，使用该发明的化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备该发明的化合物的中间体和方法。
• Protein kinase modulators and method of use
  申请人：Geuns-Meyer D. Stephanie

  公开号：US20060009453A1

  公开（公告）日：2006-01-12

  The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H 1-5 and R 1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

  本发明涉及具有通式I的化合物，其中A、B、D、E、G、H1-5和R1-4在此定义，并且合成中间体，这些化合物能够调节各种蛋白激酶受体酶，从而影响与这些激酶活性相关的各种疾病状态和条件。例如，这些化合物能够调节激酶酶，从而影响血管生成的过程，并治疗与血管生成相关的疾病和其他增生性疾病，包括癌症和炎症。本发明还包括包括这些化合物的药物组合物和治疗与蛋白激酶活性相关的疾病状态的方法。
• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20060241115A1

  公开（公告）日：2006-10-26

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等具有有效性。本发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐，以及用于预防和治疗涉及癌症等疾病和其他疾病或状况的药物组合物和方法。该发明还涉及制备此类化合物的过程，以及在此类过程中有用的中间体。
• Multi-cyclic compounds and methods of use
  申请人：Hodous Brian L.

  公开号：US20080255205A1

  公开（公告）日：2008-10-16

  The present invention relates to compounds of Formulas I and II, wherein B 1 , B 2 , B 3 , B 4 , C 1 , C 2 , ring D, L 1 , L 2 and R 1-4 are defined herein, synthetic intermediates, and pharmaceutical compositions, comprising such compounds. The compounds and compositions are capable of modulating various protein kinase receptors such as Tie-2 and Aurora and, therefore, influencing kinase related disease states and conditions. The compounds, for example, are capable of treating cancer caused by unregulated angiogenesis, and inflammation as well as other proliferative disorders.

  本发明涉及公式I和II的化合物，其中B1、B2、B3、B4、C1、C2、环D、L1、L2和R1-4在此被定义，合成中间体和包含此类化合物的制药组合物。这些化合物和组合物能够调节各种蛋白激酶受体，例如Tie-2和Aurora，从而影响激酶相关的疾病状态和情况。例如，这些化合物能够治疗由未受调节的血管生成引起的癌症和炎症以及其他增殖性疾病。
• MULTI-CYCLIC COMPOUNDS AND METHODS OF USE
  申请人：HODOUS Brian L.

  公开号：US20120245206A1

  公开（公告）日：2012-09-27

  The present invention relates to compounds of Formulas I and II, wherein B 1 , B 2 , B 3 , B 4 , C 1 , C 2 , ring D, L 1 , L 2 and R 1-4 are defined herein, synthetic intermediates, and pharmaceutical compositions, comprising such compounds. The compounds and compositions are capable of modulating various protein kinase receptors such as Tie-2 and Aurora and, therefore, influencing kinase related disease states and conditions. The compounds, for example, are capable of treating cancer caused by unregulated angiogenesis, and inflammation as well as other proliferative disorders.

  本发明涉及I和II式化合物，其中B1、B2、B3、B4、C1、C2、环D、L1、L2和R1-4在此定义，以及合成中间体和含有这些化合物的制药组合物。这些化合物和组合物能够调节各种蛋白激酶受体，如Tie-2和Aurora，从而影响激酶相关的疾病状态和条件。例如，这些化合物能够治疗由未受调节的血管生成引起的癌症和炎症以及其他增殖性疾病。