8-(2,6-Dimethylanilino)-8-oxooctanoic acid | 1211341-31-9

• 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: 8-(2,6-Dimethylanilino)-8-oxooctanoic acid
• CAS: 1211341-31-9
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: GSYUZJITHHUFRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-(2,6-Dimethylanilino)-8-oxooctanoic acid 在 lithium aluminium tetrahydride 、 silica gel 、 potassium carbonate 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 N-(2,6-dimethylphenyl)-8-oxooctanamide
  参考文献：
  名称：

  Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents

  摘要：

  The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3-7.7 mu M) comparable to vorinostat (HT1080, IC50 2.4 mu M), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.

  DOI：

  10.1007/s10593-015-1752-z
• 作为产物：
  描述：

  辛二酸 在 乙酸酐 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 8-(2,6-Dimethylanilino)-8-oxooctanoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents

  摘要：

  The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3-7.7 mu M) comparable to vorinostat (HT1080, IC50 2.4 mu M), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.

  DOI：

  10.1007/s10593-015-1752-z

文献信息

• Biological and Biophysical Properties of the Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid Are Affected by the Presence of Short Alkyl Groups on the Phenyl Ring
  作者：Frédérik Oger、Aurélien Lecorgne、Elisa Sala、Vanessa Nardese、Florence Demay、Soizic Chevance、Danielle C. Desravines、Nataliia Aleksandrova、Rémy Le Guével、Simone Lorenzi、Andrea R. Beccari、Peter Barath、Darren J. Hart、Arnaud Bondon、Daniele Carettoni、Gérard Simonneaux、Gilles Salbert

  DOI：10.1021/jm901561u

  日期：2010.3.11

  HDAC inhibitor (HDACi) is used in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the synthesis and biological evaluation of a new series of compounds derived from SAHA by substituting short alkyl chains at various positions of the phenyl ring. Such modifications induced variable effects ranging from partial loss of activity to increased potency. Through molecular modeling, we describe

  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。