5-bromo-1-(tert-butoxycarbonyl)-3-methyl-1H-pyrazolo[3,4-c]pyridine 6-oxide | 929617-44-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-bromo-1-(tert-butoxycarbonyl)-3-methyl-1H-pyrazolo[3,4-c]pyridine 6-oxide
• CAS: 929617-44-7
• 化学式: C₁₂H₁₄BrN₃O₃
• 分子量: 328.165
• InChiKey: KMUADPYMSXJWAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  19.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  71.06
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(tert-butoxycarbonyl)-3-methyl-1H-pyrazolo[3,4-c]pyridine 6-oxide 在 四(三苯基膦)钯 作用下， 以 二氯甲烷 、 xylene 为溶剂， 反应 4.0h， 生成 (S)-5-(5-(2-amino-3-phenylpropoxy)pyridin-3-yl)-3-methyl-1H-pyrazolo[3,4-c]pyridine oxide trifluoroacetic acid salt 1:3
  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：

  6-溴-4-乙基吡啶-3-胺 在 4-二甲氨基吡啶 、 溶剂黄146 、 三乙胺 、 间氯过氧苯甲酸 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 40.0h， 生成 5-bromo-1-(tert-butoxycarbonyl)-3-methyl-1H-pyrazolo[3,4-c]pyridine 6-oxide
  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