(2R)-2-(6-fluoro-5-((5-isopropoxy-1H-pyrazol-3-yl)amino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(5-fluoropyridin-2-yl)ethanol | 1073148-88-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: (2R)-2-(6-fluoro-5-((5-isopropoxy-1H-pyrazol-3-yl)amino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(5-fluoropyridin-2-yl)ethanol
• 英文别名: (2R)-2-[6-fluoro-5-[(3-propan-2-yloxy-1H-pyrazol-5-yl)amino]imidazo[4,5-b]pyridin-3-yl]-2-(5-fluoropyridin-2-yl)ethanol
• CAS: 1073148-88-5
• 化学式: C₁₉H₁₉F₂N₇O₂
• 分子量: 415.402
• InChiKey: BXERIDNAQJVEFF-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,3,6-三氟-5-硝基吡啶 在 10% Pd/C 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 21.0h， 生成 (2R)-2-(6-fluoro-5-((5-isopropoxy-1H-pyrazol-3-yl)amino)-3H-imidazo[4,5-b]pyridin-3-yl)-2-(5-fluoropyridin-2-yl)ethanol
  参考文献：
  名称：

  Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors

  摘要：

  Trk receptor tyrosine kinases have been implicated in cancer and pain. A crystal structure of TrkA with AZ-23 (1a) was obtained, and scaffold hopping resulted in two 5/6-bicyclic series comprising either imidazo[4,5-b]pyridines or purines. Further optimization of these two fusion series led to compounds with subnanomolar potencies against TrkA kinase in cellular assays. Antitumor effects in a TrkA-driven mouse allograft model were demonstrated with compounds 2d and 3a.

  DOI：

  10.1021/ml300074j

文献信息

• 5-AMINOPYRAZOL-3-YL-3H-IMIDAZO (4,5-B) PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER
  申请人：Davies Audrey

  公开号：US20100204246A1

  公开（公告）日：2010-08-12

  The present invention relates to compounds of Formula (I) and to their pharmaceutical compositions, and to their methods of use. These novel compounds provide a treatment for myeloproliferative disorders and cancer.

  本发明涉及式(I)化合物及其制药组合物，以及其使用方法。这些新型化合物为骨髓增生性疾病和癌症提供了治疗方法。
• Discovery of Disubstituted Imidazo[4,5-<i>b</i>]pyridines and Purines as Potent TrkA Inhibitors
  作者：Tao Wang、Michelle L. Lamb、Michael H. Block、Audrey Molina Davies、Yongxin Han、Ethan Hoffmann、Stephanos Ioannidis、John A. Josey、Zhong-Ying Liu、Paul D. Lyne、Terry MacIntyre、Peter J. Mohr、Charles A. Omer、Tove Sjögren、Kenneth Thress、Bin Wang、Haiyun Wang、Dingwei Yu、Hai-Jun Zhang

  DOI：10.1021/ml300074j

  日期：2012.9.13

  Trk receptor tyrosine kinases have been implicated in cancer and pain. A crystal structure of TrkA with AZ-23 (1a) was obtained, and scaffold hopping resulted in two 5/6-bicyclic series comprising either imidazo[4,5-b]pyridines or purines. Further optimization of these two fusion series led to compounds with subnanomolar potencies against TrkA kinase in cellular assays. Antitumor effects in a TrkA-driven mouse allograft model were demonstrated with compounds 2d and 3a.