5-溴-3-氯-6-硝基-1氢-吲唑 | 929617-32-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 5-溴-3-氯-6-硝基-1氢-吲唑
• 英文名称: 5-bromo-3-chloro-6-nitro-1H-indazole
• 英文别名: 5-bromo-3-chloro-6-nitro-2H-indazole
• CAS: 929617-32-3
• 化学式: C₇H₃BrClN₃O₂
• 分子量: 276.477
• InChiKey: LFBVQNHVYIPVOU-UHFFFAOYSA-N

物化性质

• 沸点：
  421.3±40.0 °C(Predicted)
• 密度：
  2.046±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-溴-3-氯-6-硝基-1氢-吲唑 在 tris(dibenzylideneacetone)dipalladium (0) 、 镍 4-二甲氨基吡啶 、 氢气 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 91.0h， 生成 (S)-tert-butyl 6-amino-5-(5-(2-(tert-butoxycarbonylamino)-3-(1H-indol-3-yl)propoxy)pyridin-3-yl)-3-chloro-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
• 作为产物：
  描述：

  4-溴-2-甲基-5-硝基苯胺 在 sodium hydroxide 、 sodium hypochlorite 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 77.0h， 生成 5-溴-3-氯-6-硝基-1氢-吲唑
  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

• NOVEL COMPOUNDS THAT ARE ERK INHIBITORS
  申请人：LIM Jongwon

  公开号：US20160068532A1

  公开（公告）日：2016-03-10

  Disclosed are the ERK inhibitors of formula (I) and the pharmaceutically acceptable salts thereof. Also disclosed are methods of treating cancer using the compounds of formula (I). This invention also provides a pharmaceutical composition comprising an effective amount of at least one compound of formula (I) and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition comprising an effective amount of at least one compound of formula (I) and an effective amount of at least one other pharmaceutically active ingredient (such as, for example, a chemotherapeutic agent), and a pharmaceutically acceptable carrier. This invention also provides a method of inhibiting ERK (i.e., inhibiting the activity of ERK2) in a patient in need of such treatment comprising administering to said patient an effective amount of at least one compound of formula (I).

  本发明涉及式(I)的ERK抑制剂及其药学上可接受的盐。还揭示了使用式(I)的化合物治疗癌症的方法。本发明还提供了一种含有至少一种式(I)化合物的有效量和药学上可接受的载体的制药组合物。本发明还提供了一种含有至少一种式(I)化合物的有效量和至少一种其他药理活性成分（例如，化疗药物）的有效量和药学上可接受的载体的制药组合物。本发明还提供了一种抑制患者ERK（即抑制ERK2活性）的方法，包括向该患者施用至少一种式(I)化合物的有效量。
• Compounds that are ERK inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10065967B2

  公开（公告）日：2018-09-04

  Disclosed are the ERK inhibitors of formula (1): and the pharmaceutically acceptable salts thereof. Also disclosed are methods of treating cancer using the compounds of formula (I).

  公开了式 (1) 的 ERK 抑制剂：及其药学上可接受的盐类。还公开了使用式（I）化合物治疗癌症的方法。
• [EN] NOVEL COMPOUNDS THAT ARE ERK INHIBITORS<br/>[FR] NOUVEAUX COMPOSÉS QUI SONT DES INHIBITEURS D'ERK
  申请人：MERCK SHARP & DOHME

  公开号：WO2014179154A3

  公开（公告）日：2015-01-29
• US9745307B2
  申请人：——

  公开号：US9745307B2

  公开（公告）日：2017-08-29
• 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.