N,N'-dimethylhexafluoroglutarimide | 662-88-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N,N'-dimethylhexafluoroglutarimide
• 英文别名: hexafluoro-glutaric acid bis-methylamide；2,2,3,3,4,4-Hexafluor-N,N'-dimethyl-glutaramid；Hexafluor-glutarsaeure-bis-methylamid；2,2,3,3,4,4-hexafluoro-N,N'-dimethylpentanediamide
• CAS: 662-88-4
• 化学式: C₇H₈F₆N₂O₂
• 分子量: 266.143
• InChiKey: CFOSYHHGYICXGG-UHFFFAOYSA-N

物化性质

• 沸点：
  332.0±42.0 °C(Predicted)
• 密度：
  1.409±0.06 g/cm3(Predicted)
• 熔点：
  144-145 °C(Solv: benzene (71-43-2))

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N'-dimethylhexafluoroglutarimide 在 lithium aluminium tetrahydride 、 三乙胺 、 邻苯三酚 作用下， 以 乙醚 、 苯 为溶剂， 反应 30.5h， 生成 N,N'-dimethyl-2,2,3,3,4,4-hexafluoropentamethylene-1,5-diacrylamide
  参考文献：
  名称：

  Neuromuscular blocking agents. Some approaches to short acting compounds

  摘要：

  A series of amidic and N-methylamidic methyl and trideuteromethyl quaternary analogues of atracurium have been prepared. All were less potent and longer acting neuromuscular blocking agents than atracurium, and all showed appreciable vagal blockade at neuromuscular blocking doses. Replacement of NCH3 by NCD3 failed to affect potency. Fluorosubstitution in the central chain did not reduce duration of action. Attachment of acyloxy substituents to the interquaternary chain of atracurium and related compounds adjacent to their ester groups shortened the duration of action significantly. Diformyloxy substitution was the most effective in reducing duration without adversely affecting other properties apart from potency, which was significantly less than that of atracurium.

  DOI：

  10.1016/0223-5234(92)90180-9
• 作为产物：
  描述：

  六氟戊二酸二甲酯 、 甲胺 在 四氢呋喃 、 乙醚 作用下， 生成 N,N'-dimethylhexafluoroglutarimide
  参考文献：
  名称：

  Fluorine-containing Secondary Diamines^1,2

  摘要：

  DOI：

  10.1021/ja01554a049

文献信息

• COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ENHANCER OF ZESTE HOMOLOG 2 POLYPEPTIDE
  申请人：Arvinas, Inc.

  公开号：US20180177750A1

  公开（公告）日：2018-06-28

  The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，其作为增强子锁定同源2的调节剂而发挥作用。具体而言，本公开涉及包含一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源2配体的双功能化合物，该配体与相应的E3泛素连接酶结合，另一端含有结合目标蛋白的基团，使目标蛋白靠近泛素连接酶以实现目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。
• ALANINE-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas, Inc.

  公开号：US20170037004A1

  公开（公告）日：2017-02-09

  The description relates to Inhibitors of Apoptosis Proteins (IAPs) binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
• Neuromuscular blocking agents. Some approaches to short acting compounds
  作者：JB Stenlake、NC Dhar、J Haddow、IM McDonald、RB Maehr、WB Wastila

  DOI：10.1016/0223-5234(92)90180-9

  日期：1992.8

  A series of amidic and N-methylamidic methyl and trideuteromethyl quaternary analogues of atracurium have been prepared. All were less potent and longer acting neuromuscular blocking agents than atracurium, and all showed appreciable vagal blockade at neuromuscular blocking doses. Replacement of NCH3 by NCD3 failed to affect potency. Fluorosubstitution in the central chain did not reduce duration of action. Attachment of acyloxy substituents to the interquaternary chain of atracurium and related compounds adjacent to their ester groups shortened the duration of action significantly. Diformyloxy substitution was the most effective in reducing duration without adversely affecting other properties apart from potency, which was significantly less than that of atracurium.
• Fluorine-containing Secondary Diamines^1,2
  作者：Burton S. Marks、George C. Schweiker

  DOI：10.1021/ja01554a049

  日期：1958.11