N-(3-(dimethylamino)propyl)-N-methyl-2-nitro-4-(trifluoromethyl)benzenamine | 926277-94-3

• 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: N-(3-(dimethylamino)propyl)-N-methyl-2-nitro-4-(trifluoromethyl)benzenamine
• 英文别名: N-(3-dimethylamino-propyl)-N-methyl-2-nitro-4-trifluoromethyl-benzenamine；N,N,N'-trimethyl-N'-[2-nitro-4-(trifluoromethyl)phenyl]propane-1,3-diamine
• CAS: 926277-94-3
• 化学式: C₁₃H₁₈F₃N₃O₂
• 分子量: 305.3
• InChiKey: LASUFHIWXJELNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(3-(dimethylamino)propyl)-N-methyl-2-nitro-4-(trifluoromethyl)benzenamine 在 钯 氢气 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 N1-(3-(二甲氨基)丙基)-N1-甲基-4-(三氟甲基)苯-1,2-二胺
  参考文献：
  名称：

  Compounds and methods of use

  摘要：

  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。

  公开号：

  US20060241115A1
• 作为产物：
  描述：

  4-氟-3-硝基三氟甲苯 、 三甲基-1,3-丙二胺 在 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以97%的产率得到N-(3-(dimethylamino)propyl)-N-methyl-2-nitro-4-(trifluoromethyl)benzenamine
  参考文献：
  名称：

  Evolution of a Highly Selective and Potent 2-(Pyridin-2-yl)-1,3,5-triazine Tie-2 Kinase Inhibitor

  摘要：

  Inhibition of angiogenesis is a promising and clinically validated approach for limiting tumor growth and survival. The receptor tyrosine kinase Tie-2 is expressed almost exclusively in the vascular endothelium and is required for developmental angiogenesis and vessel maturation. However, the significance of Tie-2 signaling in tumor angiogenesis is not well understood. In order to evaluate the therapeutic utility of inhibiting Tie-2 signaling, we developed a series of potent and orally bioavailable small molecule Tie-2 kinase inhibitors with selectivity over other kinases, especially those that are believed to be important for tumor angiogenesis. Our earlier work provided pyridinyl pyrimidine 6 as a potent, nonselective Tie-2 inhibitor that was designed on the basis of X-ray cocrystal structures of KDR inhibitors 34 (triazine) and 35 (nicotinamide). Lead optimization resulted in pyridinyl triazine 63, which exhibited > 30-fold selectivity over a panel of kinases, good oral exposure, and in vivo inhibition of Tie-2 phosphorylation.

  DOI：

  10.1021/jm061107l

文献信息

• 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。
• Alkynylpyrimidine Amide Derivatives as Potent, Selective, and Orally Active Inhibitors of Tie-2 Kinase
  作者：Victor J. Cee、Brian K. Albrecht、Stephanie Geuns-Meyer、Paul Hughes、Steve Bellon、James Bready、Sean Caenepeel、Stuart C. Chaffee、Angela Coxon、Maurice Emery、Jenne Fretland、Paul Gallant、Yan Gu、Brian L. Hodous、Doug Hoffman、Rebecca E. Johnson、Richard Kendall、Joseph L. Kim、Alexander M. Long、David McGowan、Michael Morrison、Philip R. Olivieri、Vinod F. Patel、Anthony Polverino、David Powers、Paul Rose、Ling Wang、Huilin Zhao

  DOI：10.1021/jm061112p

  日期：2007.2.1

  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.
• WO2008/57280
  申请人：——

  公开号：——

  公开（公告）日：——