4-Fluoro-2-(2-fluoro-4-iodoanilino)-6-[3-(pyrrolidin-1-ylsulfonylamino)phenoxy]benzamide | 1192453-96-5

• 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-iodoanilino)-6-[3-(pyrrolidin-1-ylsulfonylamino)phenoxy]benzamide
• CAS: 1192453-96-5
• 化学式: C₂₃H₂₁F₂IN₄O₄S
• 分子量: 614.411
• InChiKey: SHOKFLCYBWAJOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氟-4-碘苯胺 在 异丁酰胺 、 caesium carbonate 、 N,N-二异丙基乙胺 、 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-iodoanilino)-6-[3-(pyrrolidin-1-ylsulfonylamino)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 PHENOXYBENZAMIDES
  申请人：Hitchcock Marion

  公开号：US20110039819A1

  公开（公告）日：2011-02-17

  The present invention relates to substituted phenoxybenzamide compounds of general formula (I): in which R 1 , R 2 , R 3 , R 4 , R 5 , X, R 6 and q are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的取代苯氧基苯甲酰胺化合物，其中R1、R2、R3、R4、R5、X、R6和q在权利要求中定义，以及制备该化合物的方法、包含该化合物的药物组合物和制造用于治疗或预防疾病，特别是高增殖和/或血管生成紊乱的药物组合物的药用化合物的用途，作为唯一药剂或与其他活性成分组合使用。
• [EN] SUBSTITUTED PHENOXYBENZAMIDES<br/>[FR] PHÉNOXYBENZAMIDES SUBSTITUÉS
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2009129938A1

  公开（公告）日：2009-10-29

  The present invention relates to substituted phenoxybenzamide compounds of general formula (I) : in which R1, R2, R3, R4, R5, X, R6 and q are as defined in the claims, to methods of preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and /or angiogenesis disorder, 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.