(R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol | 1073149-19-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol
• 英文别名: (2R)-2-((5-fluoro-6-((5-isopropoxy-1H-pyrazol-3-yl)amino)-3-nitropyridin-2-yl)amino)-2-(5-fluoropyridin-2-yl)ethanol；(2R)-2-({5-Fluoro-6-[(5-isopropoxy-1H-pyrazol-3-yl)-amino]-3-nitropyridin-2-yl}amino)-2-(5-fluoropyridin-2-yl)-ethanol；(2R)-2-[[5-fluoro-3-nitro-6-[(3-propan-2-yloxy-1H-pyrazol-5-yl)amino]pyridin-2-yl]amino]-2-(5-fluoropyridin-2-yl)ethanol
• CAS: 1073149-19-5
• 化学式: C₁₈H₁₉F₂N₇O₄
• 分子量: 435.39
• InChiKey: BSETVYRKMLLDNH-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol 、 醋酸甲脒 在 10% Pd/C 、 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 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
• 作为产物：
  描述：

  2,3,6-三氟吡啶 在 硫酸 、 硝酸 、 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 17.5h， 生成 (R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-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
• 作为试剂：
  描述：

  、 (R)-2-(5,6-difluoro-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol 、 5-异丙氧基-1H-吡咯-3-胺 在 (R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol 、 乙酸乙酯 、 hexanes 作用下， 以to provide the title compound as a yellow solid (300 mg, 26% isolated yield)的产率得到(R)-2-(5-fluoro-6-(5-isopropoxy-1H-pyrazol-3-ylamino)-3-nitropyridin-2-ylamino)-2-(5-fluoropyridin-2-yl)ethanol
  参考文献：
  名称：

  5-AMINOPYRAZOL-3-YL-3H-IMIDAZO (4,5-B) PYRIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER

  摘要：

  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。

  公开号：

  US20100204246A1