4-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-(2-oxo-2,3-dihydro-benzooxazol-5-yloxy)-benzamide | 1226911-86-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-(2-oxo-2,3-dihydro-benzooxazol-5-yloxy)-benzamide
• 英文别名: 4-fluoro-2-(2-fluoro-4-iodoanilino)-6-[(2-oxo-3H-1,3-benzoxazol-5-yl)oxy]benzamide
• CAS: 1226911-86-9
• 化学式: C₂₀H₁₂F₂IN₃O₄
• 分子量: 523.234
• InChiKey: WUKAUWACUXJAGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氟-4-碘苯胺 在 caesium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-(2-oxo-2,3-dihydro-benzooxazol-5-yloxy)-benzamide
  参考文献：
  名称：

  Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories

  摘要：

  Using PD325901 as a starting point for identifying novel allosteric MEK inhibitors with high cell potency and long-lasting target inhibition in vivo, truncation of its hydroxamic ester headgroup was combined with incorporation of alkyl and aryl ethers at the neighboring ring position. Whereas alkoxy side chains did not yield sufficient levels of cell potency, specifically substituted aryloxy groups allowed for high enzymatic and cellular potencies. Sulfamide 28 was identified as a highly potent MEK inhibitor with nanomolar cell potency against B-RAF (V600E) as well as Ras-mutated cell lines, high metabolic stability and resulting long half-lives. It was efficacious against B-RAF as well as K-Ras driven xenograft models and showed-despite being orally bioavailable and not a P-glycoprotein substrate-much lower brain/plasma exposure ratios than PD325901. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.028

文献信息

• SUBSTITUTED AMIDO PHENOXYBENZAMIDES
  申请人：Hartung Ingo

  公开号：US20110237592A1

  公开（公告）日：2011-09-29

  The present invention relates to substituted amido phenoxybenzamide compounds of general formula (I): in which A, R1, R2, R3, R4, R5, R6, R7, R8, R9 and n are as defined in the claims, to pharmaceutical compositions and combinations containing said compounds, to methods of preparing said compounds, and to the use of said compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式（I）的取代氨基苯氧基苯酰胺化合物，其中A，R1，R2，R3，R4，R5，R6，R7，R8，R9和n如权利要求所定义，以及包含所述化合物的制药组合物和组合物，制备所述化合物的方法以及使用所述化合物或组合物治疗增生性和/或血管生成障碍的用途，作为单一制剂或与其他活性成分组合使用。
• [EN] SUBSTITUTED AMIDO PHENOXYBENZAMIDES<br/>[FR] AMIDO PHÉNOXYBENZAMIDES SUBSTITUÉS
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2010051935A2

  公开（公告）日：2010-05-14

  The present invention relates to substituted amido phenoxybenzamide compounds of general formula (I) in which A, R1, R2, R3, R4, R5, R6, R7, R8, R9 and n are as defined in the claims, to pharmaceutical compositions and combinations containing said compounds, to methods of preparing said compounds, and to the use of said compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
• Optimization of allosteric MEK inhibitors. Part 1: Venturing into underexplored SAR territories
  作者：Ingo V. Hartung、Marion Hitchcock、Florian Pühler、Roland Neuhaus、Arne Scholz、Stefanie Hammer、Kirstin Petersen、Gerhard Siemeister、Dominic Brittain、Roman C. Hillig

  DOI：10.1016/j.bmcl.2013.02.028

  日期：2013.4

  Using PD325901 as a starting point for identifying novel allosteric MEK inhibitors with high cell potency and long-lasting target inhibition in vivo, truncation of its hydroxamic ester headgroup was combined with incorporation of alkyl and aryl ethers at the neighboring ring position. Whereas alkoxy side chains did not yield sufficient levels of cell potency, specifically substituted aryloxy groups allowed for high enzymatic and cellular potencies. Sulfamide 28 was identified as a highly potent MEK inhibitor with nanomolar cell potency against B-RAF (V600E) as well as Ras-mutated cell lines, high metabolic stability and resulting long half-lives. It was efficacious against B-RAF as well as K-Ras driven xenograft models and showed-despite being orally bioavailable and not a P-glycoprotein substrate-much lower brain/plasma exposure ratios than PD325901. (C) 2013 Elsevier Ltd. All rights reserved.