8-(hydroxyamino)-8-oxo-N-(m-tolyl)octanamide | 1211341-03-5

• 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: 8-(hydroxyamino)-8-oxo-N-(m-tolyl)octanamide
• 英文别名: N'-hydroxy-N-(3-methylphenyl)octanediamide
• CAS: 1211341-03-5
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: LWXNVKYRDMMGBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 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 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 8-(hydroxyamino)-8-oxo-N-(m-tolyl)octanamide
  参考文献：
  名称：

  组蛋白脱乙酰基酶抑制剂Suberoylanilide异羟肟酸的生物和生物物理特性受苯基环上短烷基的存在影响

  摘要：

  组蛋白脱乙酰基酶（HDACs）的抑制导致肿瘤细胞系的生长停滞，分化或凋亡，这表明HDACs是癌症治疗的有希望的靶标。目前，只有一种HDAC抑制剂（HDACi）用于治疗：磺酰苯胺异羟肟酸（SAHA）。在这里，我们描述了由SAHA衍生的一系列新化合物的合成和生物学评估，方法是通过在苯环的各个位置上取代短烷基链。这种修饰引起可变的作用，其范围从活性的部分丧失到效力的增加。通过分子建模，我们描述了HDAC7脯氨酸809（仅在第2类酶中严格保守的残基）与HDACi的酰胺基团之间的可能相互作用，而核磁共振实验表明，二甲基m-取代可以使抑制剂稳定在活性位点。我们的数据提供了有关HDACi的结构活性关系的新颖信息，并提出了开发第二代SAHA样分子的新方法。

  DOI：

  10.1021/jm901561u

文献信息

• ALPHA AMINOACID ESTER-DRUG CONJUGATES HYDROLYSABLE BY CARBOXYLESTERASE
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3530290A1

  公开（公告）日：2019-08-28

  Covalent conjugation of an alpha amino acid ester to a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by intracellular carboxylesterase enzyme hCE1 and not by hCE2 or hCE3 to the corresponding acid, leads to selective accumulation of the carboxylic acid hydrolysis product in monocyte/macrophage cell and enables improved or more prolonged enzyme or receptor modulation in those cells relative to the unconjugated modulator.

  将α-氨基酸酯与细胞内目标酶或受体活性调节剂共价共轭，其中共轭物的酯基可被细胞内羧基酯酶hCE1水解为相应的酸，而不能被hCE2或hCE3水解为相应的酸、导致羧酸水解产物在单核细胞/巨噬细胞中选择性积累，与未共轭的调节剂相比，可改善或延长对这些细胞中酶或受体的调节。
• Detection of Histone Deacetylase Inhibition
  申请人：Ronen Sabrina M.

  公开号：US20110312007A1

  公开（公告）日：2011-12-22

  Provided are compositions and methods for intracellular detection of enzyme activity. One example of a composition is a histone deacetylase substrate comprising a compound of the following formula (I): One example of a method is a method for detecting histone deacetylase activity comprising introducing a compound according to formula (I) to a plurality of cells and monitoring the cells with magnetic resonance spectroscopy.
• 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.