2-chloro-4-(2-chloropyridin-3-yl)-5-fluoropyrimidine | 870221-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-4-(2-chloropyridin-3-yl)-5-fluoropyrimidine
• 英文别名: 2-Chloro-4-(2-chloro-pyridin-3-yl)-5-fluoro-pyrimidine
• CAS: 870221-54-8
• 化学式: C₉H₄Cl₂FN₃
• 分子量: 244.055
• InChiKey: QZYBSJPGQYTMLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(2-chloropyridin-3-yl)-5-fluoropyrimidine 、 盐酸甲胺 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 生成 [4-(2-chloro-pyridin-3-yl)-5-fluoro-pyrimidin-2-yl]-methyl-amine
  参考文献：
  名称：

  [EN] NITROGENATED HETEROCYCLIC DERIVATIVES AS PROTEIN KINASE MODULATORS AND USE FOR THE TREATMENT OF ANGIOGENESIS AND CANCER
  [FR] MODULATEURS DE PROTEINES KINASES ET PROCEDE D'UTILISATION

  摘要：

  公开号：

  WO2005113494A3
• 作为产物：
  描述：

  2,4-二氯-5-氟嘧啶 、 2-氯吡啶-3-硼酸 在 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 18.0h， 以66%的产率得到2-chloro-4-(2-chloropyridin-3-yl)-5-fluoropyrimidine
  参考文献：
  名称：

  Discovery of a Potent, Selective, and Orally Bioavailable Pyridinyl-Pyrimidine Phthalazine Aurora Kinase Inhibitor

  摘要：

  The discovery of aurora kinases as essential regulators of cell division has led to intense interest in identifying small molecule aurora kinase inhibitors for the potential treatment of cancer. A high-throughput screening effort identified pyridinyl-pyrimidine 6a as a moderately potent dual inhibitor of aurora kinases -A and -B. Optimization of this hit resulted in an anthranilamide lead (6j) that possessed improved enzyme and cellular activity and exhibited a high level of kinase selectivity. However, this anthranilamide and subsequent analogues suffered from a lack of oral bioavailability. Converting the internally hydrogen-bonded six-membered pseudo-ring of the anthranilamide to a phthalazine (8a-b) led to a dramatic improvement in oral bioavailability (38-61%F) while maintaining the potency and selectivity characteristics of the anthranilamide series. In a COLO 205 tumor pharmacodynamic assay measuring phosphorylation of the aurora-B substrate histone H3 at serine 10 (p-histone H3), oral administration of 86 at 50 mg/kg demonstrated significant reduction in tumor p-histone H3 for at least 6 h.

  DOI：

  10.1021/jm100394y

文献信息

• 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。
• PROTEIN KINASE MODULATORS AND METHOD OF USE
  申请人：GEUNS-MEYER Stephanie D.

  公开号：US20110201602A1

  公开（公告）日：2011-08-18

  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 proliferative 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.

  本发明涉及具有一般式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，并因此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，从而影响血管生成过程，治疗与血管生成相关的疾病和其他增殖性疾病，包括癌症和炎症。本发明还包括包括这些化合物的制药组合物和治疗与蛋白激酶活性相关的疾病状态的方法。
• NITROGENATED HETEROCYCLIC DERIVATIVES AS PROTEIN KINASE MODULATORS AND USE FOR THE TREATMENT OF ANGIOGENESIS AND CANCER
  申请人：AMGEN INC.

  公开号：EP1751136A2

  公开（公告）日：2007-02-14
• US7880000B2
  申请人：——

  公开号：US7880000B2

  公开（公告）日：2011-02-01
• US8476434B2
  申请人：——

  公开号：US8476434B2

  公开（公告）日：2013-07-02