tert-butyl 5-bromo-3-chloro-6-nitro-1H-indazole-1-carboxylate | 929617-40-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: tert-butyl 5-bromo-3-chloro-6-nitro-1H-indazole-1-carboxylate
• 英文别名: tert-Butyl 5-bromo-3-chloro-6-nitro-1H-indazole-1-carboxylate；tert-butyl 5-bromo-3-chloro-6-nitroindazole-1-carboxylate
• CAS: 929617-40-3
• 化学式: C₁₂H₁₁BrClN₃O₄
• 分子量: 376.594
• InChiKey: PTMJGFHUDOTPON-UHFFFAOYSA-N

物化性质

• 沸点：
  451.6±55.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-bromo-3-chloro-6-nitro-1H-indazole-1-carboxylate 在 tris(dibenzylideneacetone)dipalladium (0) 、 镍 氢气 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.0h， 生成 (S)-5-(5-(2-amino-3-(1H-indol-3-yl)propoxy)pyridin-3-yl)-3-chloro-1H-indazol-6-amine trifluoroacetic acid salt 1:3.1
  参考文献：
  名称：

  Design and synthesis of pyridine–pyrazolopyridine-based inhibitors of protein kinase B/Akt

  摘要：

  Thr-211 is one of three different amino acid residues in the kinase domain of protein kinase B/Akt as compared to protein kinase A (PKA), a closely related analog in the same AGC family. In an attempt to improve the potency and selectivity of our indazole-pyridine series of Akt inhibitors over PKA, efforts have focused on the incorporation of a chemical functionality to interact with the hydroxy group of Thr-211. Several substituents including an oxygen anion, amino, and nitro groups have been introduced at the C-6 position of the indazole scaffold, leading to a significant drop in Akt potency. Incorporation of a nitrogen atom into the phenyl ring at the same position (i.e., 9f) maintained the Akt activity and, in some cases, improved the selectivity over PKA. The structure-activity relationships of the new pyridine-pyrazolopyridine series of Akt inhibitors and their structural features when bound to PKA are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.010
• 作为产物：
  描述：

  4-溴-2-甲基-5-硝基苯胺 在 4-二甲氨基吡啶 、 sodium hydroxide 、 sodium hypochlorite 、 溶剂黄146 、 三乙胺 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 反应 92.0h， 生成 tert-butyl 5-bromo-3-chloro-6-nitro-1H-indazole-1-carboxylate
  参考文献：
  名称：

  Design and synthesis of pyridine–pyrazolopyridine-based inhibitors of protein kinase B/Akt

  摘要：

  Thr-211 is one of three different amino acid residues in the kinase domain of protein kinase B/Akt as compared to protein kinase A (PKA), a closely related analog in the same AGC family. In an attempt to improve the potency and selectivity of our indazole-pyridine series of Akt inhibitors over PKA, efforts have focused on the incorporation of a chemical functionality to interact with the hydroxy group of Thr-211. Several substituents including an oxygen anion, amino, and nitro groups have been introduced at the C-6 position of the indazole scaffold, leading to a significant drop in Akt potency. Incorporation of a nitrogen atom into the phenyl ring at the same position (i.e., 9f) maintained the Akt activity and, in some cases, improved the selectivity over PKA. The structure-activity relationships of the new pyridine-pyrazolopyridine series of Akt inhibitors and their structural features when bound to PKA are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.010

文献信息

• Design and synthesis of pyridine–pyrazolopyridine-based inhibitors of protein kinase B/Akt
  作者：Gui-Dong Zhu、Jianchun Gong、Viraj B. Gandhi、Keith Woods、Yan Luo、Xuesong Liu、Ran Guan、Vered Klinghofer、Eric F. Johnson、Vincent S. Stoll、Mulugeta Mamo、Qun Li、Saul H. Rosenberg、Vincent L. Giranda

  DOI：10.1016/j.bmc.2007.01.010

  日期：2007.3

  Thr-211 is one of three different amino acid residues in the kinase domain of protein kinase B/Akt as compared to protein kinase A (PKA), a closely related analog in the same AGC family. In an attempt to improve the potency and selectivity of our indazole-pyridine series of Akt inhibitors over PKA, efforts have focused on the incorporation of a chemical functionality to interact with the hydroxy group of Thr-211. Several substituents including an oxygen anion, amino, and nitro groups have been introduced at the C-6 position of the indazole scaffold, leading to a significant drop in Akt potency. Incorporation of a nitrogen atom into the phenyl ring at the same position (i.e., 9f) maintained the Akt activity and, in some cases, improved the selectivity over PKA. The structure-activity relationships of the new pyridine-pyrazolopyridine series of Akt inhibitors and their structural features when bound to PKA are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.