Vorinostat

• 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: Vorinostat
• 英文别名: N-cyclohexyl-N'-hydroxyoctanediamide
• 化学式: C₁₄H₂₆N₂O₃
• 分子量: 270.372
• InChiKey: ATGOFQDKNRCCKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 Vorinostat
  参考文献：
  名称：

  Precursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus Chalara sp.

  摘要：

  植物内生真菌 Chalara sp. 能够将表观遗传修饰剂 vorinostat 生物转化为形成独特的含苯胺的聚酮类化合物，被命名为 chalanilines。在这里，我们试图通过改变前体 vorinostat 中的苯胺基团来扩展 chalaniline A 类分子的化学多样性。总共，通过两步合成制备了二十三种不同的 vorinostat 类似物，其中十九种被真菌转化为聚酮类化合物。选择产量最高的底物进行大规模前体导向生物合成，分离、纯化并结构表征了五种新化合物，包括两种氟代 chalanilines。结构阐明依赖于一维和二维核磁共振技术，并得到低分辨率和高分辨率质谱的支持。所有化合物均进行了生物活性测试，但在抗微生物或细胞存活率测定中均不活跃。含氨基富烯的天然产物很少见，而这种高产率的前体导向过程允许对这类化合物进行多样化。

  DOI：

  10.3390/molecules26154418

文献信息

• COMPOUNDS AND METHODS FOR IMPROVING IMPAIRED ENDOGENOUS FIBRINOLYSIS USING HISTONE DEACETYLASE INHIBITORS
  申请人：Larsson Pia

  公开号：US20140051716A1

  公开（公告）日：2014-02-20

  There is provided a compound which is a histone deacetylase (HDAC) inhibitor, or a pharmaceutically acceptable ester, amide, solvate or salt thereof, for use in: (I) treating or preventing a pathological condition associated with excess fibrin deposition and/or thrombus formation; and/or (II) potentiating the degradation of fibrin deposits and preventing such deposits associated with pathological conditions or which may lead to such conditions, wherein the HDAC inhibitor, and the dose thereof, is as described in the description. There is also provided valproic acid, or a pharmaceutically acceptable salt thereof, for use in improving or normalizing endogenous fibrinolysis impaired by local or systemic inflammation.
• Precursor-Directed Biosynthesis of Aminofulvenes: New Chalanilines from Endophytic Fungus Chalara sp.
  作者：Mahsa Khoshbakht、Jason Srey、Donovon A. Adpressa、Annika Jagels、Sandra Loesgen

  DOI：10.3390/molecules26154418

  日期：——

  The plant endophyte Chalara sp. is able to biotransform the epigenetic modifier vorinostat to form unique, aniline-containing polyketides named chalanilines. Here, we sought to expand the chemical diversity of chalaniline A-type molecules by changing the aniline moiety in the precursor vorinostat. In total, twenty-three different vorinostat analogs were prepared via two-step synthesis, and nineteen were incorporated by the fungus into polyketides. The highest yielding substrates were selected for large-scale precursor-directed biosynthesis and five novel compounds, including two fluorinated chalanilines, were isolated, purified, and structurally characterized. Structure elucidation relied on 1D and 2D NMR techniques and was supported by low- and high-resolution mass spectrometry. All compounds were tested for their bioactivity but were not active in antimicrobial or cell viability assays. Aminofulvene-containing natural products are rare, and this high-yielding, precursor-directed process allows for the diversification of this class of compounds.

  植物内生真菌 Chalara sp. 能够将表观遗传修饰剂 vorinostat 生物转化为形成独特的含苯胺的聚酮类化合物，被命名为 chalanilines。在这里，我们试图通过改变前体 vorinostat 中的苯胺基团来扩展 chalaniline A 类分子的化学多样性。总共，通过两步合成制备了二十三种不同的 vorinostat 类似物，其中十九种被真菌转化为聚酮类化合物。选择产量最高的底物进行大规模前体导向生物合成，分离、纯化并结构表征了五种新化合物，包括两种氟代 chalanilines。结构阐明依赖于一维和二维核磁共振技术，并得到低分辨率和高分辨率质谱的支持。所有化合物均进行了生物活性测试，但在抗微生物或细胞存活率测定中均不活跃。含氨基富烯的天然产物很少见，而这种高产率的前体导向过程允许对这类化合物进行多样化。