methyl 8-oxo-8-[(4-phenoxyphenyl)amino]octanoate | 1326750-54-2

• 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: methyl 8-oxo-8-[(4-phenoxyphenyl)amino]octanoate
• 英文别名: Methyl 8-oxo-8-[(4-phenoxyphenyl)amino]octanoate；methyl 8-oxo-8-(4-phenoxyanilino)octanoate
• CAS: 1326750-54-2
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: CXFXFOPIJNCHIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 8-oxo-8-[(4-phenoxyphenyl)amino]octanoate 在 N-氯代丁二酰亚胺 、 lithium aluminium tetrahydride 、 盐酸羟胺 、 sodium acetate 、 silica gel 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 (Z)-8-(aziridin-1-yl)-8-(hydroxyimino)-N-(4-phenoxyphenyl)octanamide
  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 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 methyl 8-oxo-8-[(4-phenoxyphenyl)amino]octanoate
  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

• Synthesis and Importance of Bulky Aromatic Cap of Novel SAHA Analogs for HDAC Inhibition and Anticancer Activity
  作者：Pu-Soon Chun、Won-Hee Kim、Jung-Su Kim、Jin-Ah Kang、Hye-Jin Lee、Ji-Young Park、Mee-Young Ahn、Hyung-Sik Kim、Hyung-Ryong Moon

  DOI：10.5012/bkcs.2011.32.6.1891

  日期：2011.6.20

  On the basis of potent HDAC-inhibitory activity and anticancer activity of SAHA, novel SAHA derivatives 3a-d and 7 with a bulky cap such as p-dimethylaminophenyl, 4-phenylaminophenyl, 4-phenyloxyphenyl, 9H-fluorenyl or naphthalenyl ring were synthesized starting from the corresponding aryl amines or naphthalenyl acetic acid using an EDC-mediated amide coupling reaction in the presence of HOBt followed by a nucleophilic addition-elimination reaction with hydroxylamine. Compounds 3b, 3c and 3d showed more potent inhibitory activity on total HDACs (14~27-fold), HDAC1 (8~15-fold), HDAC2 (1.3~25-fold) and HDAC7 (1~3-fold) and more potent anticancer activity (2~22-fold) against MCF-7, MDA-MB-231, MCF-7/Dox, MCF-7/Tam, SK-OV-3, LNCaP and PC3 human cancer cell lines than SAHA.

  基于SAHA的强效HDAC抑制活性和抗癌活性，通过EDC介导的酰胺偶联反应以及随后与羟胺的亲核加成-消除反应，从相应的芳基胺或萘乙酸出发，合成了具有大体积帽结构的新型SAHA衍生物3a-d和7，例如邻二甲氨基苯基、邻苯胺基苯基、邻苯氧基苯基、9H-芴基或萘基环。化合物3b、3c和3d显示出比SAHA更强的总HDACs（14~27倍）、HDAC1（8~15倍）、HDAC2（1.3~25倍）和HDAC7（1~3倍）抑制活性，以及对MCF-7、MDA-MB-231、MCF-7/Dox、MCF-7/Tam、SK-OV-3、LNCaP和PC3人癌细胞系更强的抗癌活性（2~22倍）。