N1-(4-(dimethylamino)phenyl)-N8-hydroxyoctanediamide | 1219807-91-6

• 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: N1-(4-(dimethylamino)phenyl)-N8-hydroxyoctanediamide
• 英文别名: N-[4-(dimethylamino)phenyl]-N'-hydroxyoctanediamide
• CAS: 1219807-91-6
• 化学式: C₁₆H₂₅N₃O₃
• 分子量: 307.393
• InChiKey: BFRIBJACCUKTCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  methyl 8-(4-(dimethylamino)phenylamino)-8-oxooctanoate 在 羟胺 作用下， 以 甲醇 、 水 为溶剂， 以57%的产率得到N1-(4-(dimethylamino)phenyl)-N8-hydroxyoctanediamide
  参考文献：
  名称：

  Synthesis and Importance of Bulky Aromatic Cap of Novel SAHA Analogs for HDAC Inhibition and Anticancer Activity

  摘要：

  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）。

  DOI：

  10.5012/bkcs.2011.32.6.1891

文献信息

• Modified Cap Group Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivatives Reveal Improved Selective Antileukemic Activity
  作者：Chanaz Salmi-Smail、Aurélie Fabre、Franck Dequiedt、Audrey Restouin、Rémy Castellano、Slaveia Garbit、Philippe Roche、Xavier Morelli、Jean Michel Brunel、Yves Collette

  DOI：10.1021/jm901358y

  日期：2010.4.22

  A series of SAHA cap derivatives was designed and prepared in good-to-excellent yields that varied from 49% to 95%. These derivatives were evaluated for their antiproliferative activity in several human cancer cell lines. Antiproliferative activity was observed for concentrations varying from 0.12 to > 100 mu M, and a molecular modeling approach of selected SAHA derivatives, based on available structural information of human HDAC8 in complex with SAHA, was performed. Strikingly, two compounds displayed up to 10-fold improved antileukemic activity with respect to SAHA; however, these compounds displayed antiproliferative activity similar to SAHA when assayed against solid tumor-derived cell lines. A 10-fold improvement in the leukemic vs peripheral blood mononuclear cell therapeutic ratio, with no evident in vivo toxicity toward blood cells, was also observed. The herein-described compounds and method of synthesis will provide invaluable tools to investigate the molecular mechanism responsible for the reported selectively improved antileukemic activity.
• 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）。