4-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-phenoxy-benzamide | 1084332-31-9

• 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: 4-fluoro-2-(2-fluoro-4-iodo-phenylamino)-6-phenoxy-benzamide
• 英文别名: 4-Fluoro-2-(2-fluoro-4-iodoanilino)-6-phenoxybenzamide
• CAS: 1084332-31-9
• 化学式: C₁₉H₁₃F₂IN₂O₂
• 分子量: 466.226
• InChiKey: IAQKSUMFSKWEMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  5

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-phenoxy-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 phenylamino-benzene derivatives useful for treating hyper-proliferative disorders and diseases associated with mitogen extracellular kinase activity
  申请人：Li Yingfu

  公开号：US20090082328A1

  公开（公告）日：2009-03-26

  This invention relates to novel substituted phenylamino-benzene compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及新颖的取代苯基氨基苯化合物、含有这些化合物的药物组合物以及将这些化合物或组合物作为唯一活性成分或与其他活性成分联合使用治疗增生和/或血管生成异常的用途。
• SUBSTITUTED PHENYLAMINO-BENZENE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH MITOGEN EXTRACELLULAR KINASE ACTIVITY
  申请人：Rudolph Joachim

  公开号：US20110071125A1

  公开（公告）日：2011-03-24

  This invention relates to novel substituted phenylamino-benzene compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

  本发明涉及新型取代苯胺基苯化合物、含有这种化合物的制药组合物以及将这些化合物或组合物用于治疗增殖过度和/或血管生成障碍，作为单一药物或与其他活性成分联合使用的用途。
• SUBSTITUTED PHENYLAMINO-BENZENE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH MITOGEN EXTRACELLULAR KINASE ACTIVITY
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2155659A1

  公开（公告）日：2010-02-24
• [EN] SUBSTITUTED PHENYLAMINO-BENZENE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH MITOGEN EXTRACELLULAR KINASE ACTIVITY<br/>[FR] DÉRIVÉS DE PHÉNYLAMINO-BENZÈNE SUBSTITUÉS UTILES POUR LE TRAITEMENT DE MALADIES ET DE TROUBLES HYPERPROLIFÉRATIFS ASSOCIÉS AVEC L'ACTIVITÉ DES KINASES EXTRACELLULAIRES ACTIVÉES PAR DES MITOGÈNES
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2008138639A1

  公开（公告）日：2008-11-20

  [EN] This invention relates to novel substituted phenylamino-benzene compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper- proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients.
  [FR] L'invention concerne de nouveaux composés de phénylamino-benzène substitués, des compositions pharmaceutiques qui contiennent de tels composés et l'utilisation de ces composés ou de ces compositions pour le traitement de troubles hyperprolifératifs et/ou de l'angiogenèse, en tant qu'agent unique ou en combinaison avec d'autres ingrédients actifs.
• 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.