3-(1-cyano-1-methylethyl)-N-[3-(2-fluoro-4-nitrophenoxy)phenyl]benzamide | 1123580-71-1

• 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: 3-(1-cyano-1-methylethyl)-N-[3-(2-fluoro-4-nitrophenoxy)phenyl]benzamide
• 英文别名: 3-(2-cyanopropan-2-yl)-N-[3-(2-fluoro-4-nitrophenoxy)phenyl]benzamide
• CAS: 1123580-71-1
• 化学式: C₂₃H₁₈FN₃O₄
• 分子量: 419.412
• InChiKey: PPXCRWRHKNSGBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(1-cyano-1-methylethyl)-N-[3-(2-fluoro-4-nitrophenoxy)phenyl]benzamide 在 铁粉 、 溶剂黄146 、 calcium chloride 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 N-{3-[(2-amino-5-fluoro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(2-cyanopropan-2-yl)benzamide
  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：

  3-(1-cyano-1-methylethyl)-N-(3-hydroxyphenyl)benzamide 、 3,4-二氟硝基苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以70%的产率得到3-(1-cyano-1-methylethyl)-N-[3-(2-fluoro-4-nitrophenoxy)phenyl]benzamide
  参考文献：
  名称：

  2-Carbonylaminobenzothiazoles and their use for the prophylaxis and treatment of cancer

  摘要：

  公开号：

  EP2181987B9

文献信息

• HETEROCYCLIC COMPOUND AND USE THEREOF
  申请人：Hirose Masaaki

  公开号：US20110172245A1

  公开（公告）日：2011-07-14

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

  提供的是一种具有强烈Raf抑制活性的杂环化合物。该化合物由以下式表示：其中每个符号如规范中定义，或其盐。
• Heterocyclic compound and use thereof
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US08324395B2

  公开（公告）日：2012-12-04

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

  提供的是一种具有较强Raf抑制活性的杂环化合物。该化合物由下式所表示：其中每个符号如规范中所定义，或其盐。
• US8324395B2
  申请人：——

  公开号：US8324395B2

  公开（公告）日：2012-12-04