2-(3-aminophenoxy)-5-nitrobenzonitrile | 1079042-73-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(3-aminophenoxy)-5-nitrobenzonitrile
• CAS: 1079042-73-1
• 化学式: C₁₃H₉N₃O₃
• 分子量: 255.233
• InChiKey: JUDDBBURZSQSON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(3-aminophenoxy)-5-nitrobenzonitrile 在 吡啶 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 85.0 ℃ 、101.33 kPa 条件下， 反应 35.67h， 生成 N-{7-cyano-6-[3-({[2-(trifluoromethyl)phenyl]acetyl}amino)phenoxy]-1,3-benzothiazol-2-yl}cyclopropanecarboxamide
  参考文献：
  名称：

  Discovery of a Selective Kinase Inhibitor (TAK-632) Targeting Pan-RAF Inhibition: Design, Synthesis, and Biological Evaluation of C-7-Substituted 1,3-Benzothiazole Derivatives

  摘要：

  With the aim of discovering a selective kinase inhibitor targeting pan-RAF kinase inhibition, we designed novel 1,3-benzothiazole derivatives based on our thiazolo[5,4-b]pyridine class RAF/VEGFR2 inhibitor 1 and developed a regioselective cyclization methodology for the C-7-substituted 1,3-benzothiazole scaffold utilizing meta-substituted anilines. Eventually, we selected 7-cyano derivative 8B (TAK-632) as a development candidate and confirmed its binding mode by cocrystal structure with BRAF. Accommodation of the 7-cyano group into the BRAF-selectivity pocket and the 3-(trifluoromethyl)phenyl acetamide moiety into the hydrophobic back pocket of BRAF in the DFG-out conformation contributed to enhanced RAF potency and selectivity vs VEGFR2. Reflecting its potent pan-RAF inhibition and slow off-rate profile, 8B demonstrated significant cellular activity against mutated BRAF or mutated NRAS cancer cell lines. Furthermore, in both A375 (BRAF(V600E))and HMVII (NRAS(Q61K)) xenograft models in rats, 8B demonstrated regressive antitumor efficacy by twice daily, 14-day repetitive administration without significant body weight loss.

  DOI：

  10.1021/jm400778d
• 作为产物：
  描述：

  2-氟-5-硝基苯腈 、 3-氨基苯酚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以66%的产率得到2-(3-aminophenoxy)-5-nitrobenzonitrile
  参考文献：
  名称：

  [EN] BENZOTHIAZOLE DERIVATIVES AS ANTICANCER AGENTS
  [FR] DÉRIVÉS DE BENZOTHIAZOLE CONVENANT COMME AGENTS ANTICANCÉREUX

  摘要：

  提供了一个显示强烈Raf抑制活性的融合杂环衍生物。一个由式(I)表示的化合物，其中每个符号如本说明书中所定义，或其盐。

  公开号：

  WO2010064722A1

文献信息

• HETEROCYCLIC COMPOUND AND USE THEREOF
  申请人：OKANIWA Masanori

  公开号：US20100216810A1

  公开（公告）日：2010-08-26

  Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  提供了一种融合杂环衍生物，具有强烈的Raf抑制活性。该化合物由以下式表示： 其中每个符号如本规范中所定义，或其盐。
• Benzothiazole compounds useful for Raf inhibition
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08143258B2

  公开（公告）日：2012-03-27

  Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  提供的是一种融合杂环衍生物，具有强大的Raf抑制活性。化合物的化学式如下： 其中每个符号的定义均如本说明书中所定义的，或其盐。
• Heterocyclic compound and use thereof
  申请人：Okaniwa Masanori

  公开号：US08497274B2

  公开（公告）日：2013-07-30

  Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula wherein each symbol is as defined in the present specification, or a salt thereof.

  提供了一种融合杂环衍生物，具有强烈的Raf抑制活性。化合物的化学式表示为其中每个符号如本规范中所定义的，或其盐。
• Synthesis and anti-CVB 3 evaluation of substituted 5-nitro-2-phenoxybenzonitriles
  作者：Gerhard Pürstinger、Armando M. De Palma、Günther Zimmerhofer、Simone Huber、Sophie Ladurner、Johan Neyts

  DOI：10.1016/j.bmcl.2008.07.099

  日期：2008.9

  The synthesis and SAR of a series of 60 substituted 2-phenoxy-5-nitrobenzonitriles (analogues of MDL-860) as inhibitors of enterovirus replication (in particular of coxsackievirus B3 (CVB 3)) are reported. Several of the analogues inhibited CVB 3 and other enteroviruses at low-micromolar concentrations. (C) 2008 Elsevier Ltd. All rights reserved.
• BENZOTHIAZOLE DERIVATIVES AS ANTICANCER AGENTS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2358689B1

  公开（公告）日：2015-09-30