2-chloro-2'-fluoro-[3,4']bipyridinyl | 870221-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-chloro-2'-fluoro-[3,4']bipyridinyl
• 英文别名: 2-Chloro-2'-fluoro-3,4'-bipyridine；2-chloro-3-(2-fluoropyridin-4-yl)pyridine
• CAS: 870221-45-7
• 化学式: C₁₀H₆ClFN₂
• 分子量: 208.622
• InChiKey: AHZUKRIVCWRDDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 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：
  25.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  2-chloro-2'-fluoro-[3,4']bipyridinyl 在 potassium carbonate 、 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 21.5h， 生成 N-(5-cyclohexyl-2-methoxyphenyl)-4-methyl-3-(3-(2-(methylamino)pyridin-4-yl)pyridin-2-yloxy)benzamide
  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
• 作为产物：
  描述：

  2-氟-4-碘吡啶 、 2-氯吡啶-3-硼酸 在 palladium diacetate sodium carbonate 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以96%的产率得到2-chloro-2'-fluoro-[3,4']bipyridinyl
  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

• Aurora kinase modulators and method of use
  申请人：Cee J. Victor

  公开号：US20070185111A1

  公开（公告）日：2007-08-09

  The present invention relates to chemical compounds having a general formula I wherein A 1 , A 2 , C 1 , C 2 , D, L 1 , L 2 , Z and R 1 - 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 such kinases. For example, the compounds are capable of modulating Aurora kinase thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of Aurora kinase.

  本发明涉及具有一般式I的化合物，其中A1、A2、C1、C2、D、L1、L2、Z和R1-在此定义，并且具有调节各种蛋白激酶受体酶的能力，从而影响与这些激酶活动相关的各种疾病状态和病况。例如，这些化合物能够调节枢纽激酶，从而影响细胞周期和细胞增殖过程，用于治疗癌症和癌症相关疾病。该发明还包括含有这些化合物的药物组合物，以及治疗与枢纽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 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。
• Aurora Kinase Modulators and Method of Use
  申请人：CEE Victor J.

  公开号：US20110263530A1

  公开（公告）日：2011-10-27

  The present invention relates to chemical compounds having a general formula I wherein A 1 , A 2 , C 1 , C 2 , D, L 1 , L 2 , Z and R 3 , R 4 , R 6 , R 7 and R 8 are defined herein, which are capable of modulating Aurora kinase protein activity, thereby influencing various disease states and conditions related to the activities of Aurora kinase proteins. For example, the compounds are capable of influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, processes of preparing compounds of the invention, synthetic intermediates and methods of treatment of conditions related to the activity of Aurora kinase.

  本发明涉及具有一般式I的化合物，其中定义了A1、A2、C1、C2、D、L1、L2、Z和R3、R4、R6、R7和R8，这些化合物能够调节极化激酶蛋白活性，从而影响与极化激酶蛋白活性相关的各种疾病状态和情况。例如，这些化合物能够影响细胞周期和细胞增殖的过程，以治疗癌症和与癌症相关的疾病。本发明还包括制备本发明化合物的药物组合物、合成中间体和治疗与极化激酶活性相关疾病的方法。
• AURORA KINASE MODULATORS AND METHOD OF USE
  申请人：Amgen Inc.

  公开号：US20140066430A1

  公开（公告）日：2014-03-06

  The present invention relates to chemical compounds having a general formula I wherein A 1 , A 2 , C 1 , C 2 , D, L 1 , L 2 , Z and R 3 , R 4 , R 6 , R 7 and R 8 are defined herein, which are capable of modulating Aurora kinase protein activity, thereby influencing various disease states and conditions related to the activities of Aurora kinase proteins. For example, the compounds are capable of influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, processes of preparing compounds of the invention, synthetic intermediates and methods of treatment of conditions related to the activity of Aurora kinase.

  本发明涉及具有一般式I的化合物，其中A1，A2，C1，C2，D，L1，L2，Z和R3，R4，R6，R7和R8在此定义，这些化合物能够调节极化激酶蛋白活性，从而影响与极化激酶蛋白活动相关的各种疾病状态和病情。例如，这些化合物能够影响细胞周期和细胞增殖过程，以治疗癌症和癌症相关疾病。本发明还包括制备本发明化合物的药物组合物、合成中间体和治疗与极化激酶活性相关疾病的方法。