3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoic acid pentafluorophenyl ester | 391212-18-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoic acid pentafluorophenyl ester
• 英文别名: pentafluorophenyl 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoate；2,3,4,5,6-pentafluorophenyl-3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoate；Perfluorophenyl 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoate；(2,3,4,5,6-pentafluorophenyl) 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoate
• CAS: 391212-18-3
• 化学式: C₁₉H₆F₈INO₂
• 分子量: 559.154
• InChiKey: ZIMBAOVGRIXELL-UHFFFAOYSA-N

物化性质

• 沸点：
  500.2±50.0 °C(Predicted)
• 密度：
  1.897±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoic acid pentafluorophenyl ester 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 N-(2-aminoethoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide
  参考文献：
  名称：

  Discovery of Bifunctional Oncogenic Target Inhibitors against Allosteric Mitogen-Activated Protein Kinase (MEK1) and Phosphatidylinositol 3-Kinase (PI3K)

  摘要：

  The synthesis of a series of single entity, bifunctional MEK1/PI3K inhibitors achieved by covalent linking of structural analogs of the ATP-competitive PI3K inhibitor ZSTK474 and the ATP-noncompetitive MEK inhibitor PD0325901 is described. Inhibitors displayed potent in vitro inhibition of MEK1 (0.015 < IC50 (nM) < 56.7) and PI3K (54 < IC50 (nM) < 341) in enzymatic inhibition assays. Concurrent MEK1 and PI3K inhibition was demonstrated with inhibitors 9 and 14 in two tumor cell lines (A549, D54). Inhibitors produced dose-dependent decreased cell viability similar to the combined administration of equivalent doses of ZSTK474 and PD0325901. In vivo efficacy of 14 following oral administration was demonstrated in D54 glioma and A549 lung tumor bearing mice. Compound 14 showed a 95% and 67% inhibition of tumor ERK1/2 and Akt phosphorylation, respectively, at 2 h postadministration by Western blot analysis, confirming the bioavailability and efficacy of this bifunctional inhibitor strategy toward combined MEK1/PI3K inhibition.

  DOI：

  10.1021/acs.jmedchem.5b01655
• 作为产物：
  描述：

  2-(2-氟-4-碘苯胺)-3,4-二氟苯甲酸 、 三氟乙酸五氟苯酯 在 吡啶 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 20.5h， 以92.3%的产率得到3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoic acid pentafluorophenyl ester
  参考文献：
  名称：

  [EN] MEK INHIBITING OXA- AND THIA-DIAZOL-2-YL PHENYLAMINE DERIVATES
  [FR] DERIVES D'OXA- ET THIA-DIAZOL-2-YL PHENYLAMINE A INHIBITION DE MEK

  摘要：

  这项发明提供了取代苯基-(2-[1,3,4]噻二唑-2-基苯基)-胺和(2-[1,3,4]噁二唑-2-基苯基)苯基胺化合物，这些化合物作为MAPK/ERK激酶（'MEK'）酶的抑制剂，以及在免疫调节和治疗缓解炎症、癌症和再狭窄等增殖性疾病中使用的药物组合物和方法。

  公开号：

  WO2004056789A1

文献信息

• Oxygenated esters of 4-lodo phenylamino benzhydroxamic acids
  申请人：——

  公开号：US20040054172A1

  公开（公告）日：2004-03-18

  The present invention relates to oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof. The present invention also relates to crystaline forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.

  本发明涉及氧化酯化的4-碘苯胺基苯基羟肟酸衍生物，以及其药物组合物和使用方法。本发明还涉及氧化酯化的4-碘苯胺基苯基羟肟酸衍生物的晶体形式，药物组合物和使用方法。
• 5-Carboxyfluorescein tagged N-phenylanthranilamide as a tracer reagent for fluorescence polarization: a robust method to screen MAPK pathway allosteric inhibitors
  作者：Z. Nooshin Rezvani、R. John Mayer、Weng C. Chan

  DOI：10.1039/b925042e

  日期：——

  Fluorescence polarization using Nα-(fluorescein-5-carbonyl)-Nε-(N-[2-fluoro-4-iodophenyl]-3,4-difluoroanthraniloyl)lysyl amide is capable of rapidly identifying inhibitor ligands that bind to an allosteric site in MEK1.

  使用Nα-(荧光素-5-羧基)-Nε-(N-[2-氟-4-碘苯基]-3,4-二氟苯甲酰基)赖氨酸酰胺的荧光偏振技术能够快速识别结合到MEK1别构位点的抑制剂配体。
• MEK inhibiting compounds
  申请人：Barrett D. Stephen

  公开号：US20050004186A1

  公开（公告）日：2005-01-06

  This invention provides substituted Phenyl-(2-[1,3,4]thiadiazol-2-yl-phenyl)-amine and (2-[1,3,4]Oxadiazol-2-yl-phenyl)phenyl-amine compounds which act as inhibitors of MAPK/ERK Kinase (“MEK”) enzymes and pharmaceutical compositions and methods for their use in immunomodulation and in the treatment and alleviation of inflammation, and proliferative diseases such as cancer and restenosis.

  本发明提供了取代苯基-(2-[1,3,4]噻二唑-2-基苯基)-胺和(2-[1,3,4]噁二唑-2-基苯基)苯基胺化合物，其作为MAPK/ERK激酶（“MEK”）酶的抑制剂，并提供了在免疫调节和治疗和缓解炎症、癌症和再狭窄等增殖性疾病中使用它们的制药组合物和方法。
• Oxygenated esters of 4-iodo phenylamino benzhydroxamic acids
  申请人：Barrett Douglas Stephen

  公开号：US20050176820A1

  公开（公告）日：2005-08-11

  The present invention relates to oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof. The present invention also relates to crystalline forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.

  本发明涉及4-碘苯胺苯羟肟酸衍生物的含氧酯、制药组合物及其使用方法。本发明还涉及含氧酯的晶体形式、制药组合物及其使用方法。
• Multifunctional inhibitors of MEK/PI3K and mTOR/MEK/PI3K biological pathways and therapeutic methods using the same
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US10919877B2

  公开（公告）日：2021-02-16

  Multifunctional inhibitors of mTOR, MEK, and PI3K and compositions containing the same are disclosed. Methods of using the multifunctional inhibitors in the treatment of diseases and conditions wherein inhibition of one or more of mTOR, MEK, and PI3K provides a benefit, like cancers, also are disclosed.

  本发明公开了mTOR、MEK和PI3K的多功能抑制剂以及含有这些抑制剂的组合物。还公开了使用多功能抑制剂治疗疾病和病症的方法，在这些疾病和病症中，抑制 mTOR、MEK 和 PI3K 中的一种或多种可带来益处，如癌症。