benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate | 1355356-58-9

• 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: benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate
• 英文别名: Benzyl 8-chloro-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-8-oxooctanoate；benzyl 8-chloro-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-8-oxooctanoate
• CAS: 1355356-58-9
• 化学式: C₁₅H₇ClF₁₂O₃
• 分子量: 498.653
• InChiKey: JYABTVZCSMKRTG-UHFFFAOYSA-N

物化性质

• 沸点：
  90-92 °C
• 密度：
  1.580±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate 在 羟胺 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluorooctanedioic acid hydroxyamide (4-phenylthiazol-2-yl)amide
  参考文献：
  名称：

  Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases

  摘要：

  Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class 11, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.041
• 作为产物：
  描述：

  全氟木酸二水合物 在 N,N-二甲基甲酰胺 氯化亚砜 作用下， 反应 6.0h， 生成 benzyl 7-chlorocarbonyl-2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptanoate
  参考文献：
  名称：

  [EN] HISTONE DEACETYLASE (HDAC) INHIBITING COMPOUNDS AND METHOD OF MAKING SAME
  [FR] COMPOSÉS INHIBANT L'HISTONE DÉSACÉTYLASE (HDAC) ET PROCÉDÉ DE FABRICATION DE CEUX-CI

  摘要：

  该发明涉及新型HDAC抑制剂及制备这种HDAC抑制剂的方法。本发明提供了具有全氟化连接剂的新型HDAC抑制剂，该连接剂位于金属结合基团和帽基团之间。

  公开号：

  WO2012107304A1

文献信息

• Perfluorinated hydroxamic acids are potent and selective inhibitors of HDAC-like enzymes from Pseudomonas aeruginosa
  作者：Christian Meyners、Benjamin Wolff、Alexander Kleinschek、Andreas Krämer、Franz-Josef Meyer-Almes

  DOI：10.1016/j.bmcl.2017.02.050

  日期：2017.4

  A series of perfluorinated SAHA (PFSAHA) was prepared and profiled against a panel of human and bacterial members of the Histone deacetylase (HDAC) family. Some of the active substances show nanomolar inhibitory activity and several hundred fold selectivity for the HDAC like enzyme PA3774 from P. aeruginosa. The extraordinary selectivity against human HDACs results from the distinct oligomeric state of PA3774 which consists of two head-to-head dimers. The binding pocket is defined by the surface of both opposite monomers confining the access of ligands to the active site. In addition, the aromatic cap group of PFSAHA undergoes an edge-to-face aromatic interaction with phenylalanine from the opposite monomer. (C) 2017 Elsevier Ltd. All rights reserved.
• Histone deacetylase (HDAC) inhibiting compounds and method of making same
  申请人：Dr. Felix Jäger und Dr. Stefan Drinkuth Laborgemeinschaft OHG

  公开号：EP2486923B1

  公开（公告）日：2015-09-09