N⁶-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N²-(5-methyl-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine | 1079275-64-1

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: N⁶-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N²-(5-methyl-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine
• 英文别名: 6-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-2-N-(5-methyl-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine
• CAS: 1079275-64-1
• 化学式: C₁₅H₁₅FN₈O₂
• 分子量: 358.335
• InChiKey: LQFBNSGJPAUXRV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N⁶-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N²-(5-methyl-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine 、 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 N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-3-(5-methyl-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridin-5-amine
  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：

  2,6-二氯-3-硝基吡啶 在 N,N-二异丙基乙胺 作用下， 以 乙腈 、 正丁醇 为溶剂， 反应 28.0h， 生成 N⁶-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-N²-(5-methyl-1H-pyrazol-3-yl)-3-nitropyridine-2,6-diamine
  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

• 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.