1-amino-4-{N-[2,4,6-(trimethyl)benzenesulfonyl]}-8-{N-[4-(tert-butyl)benzyl]-N-[2,4,6-(trimethyl)benzenesulfonyl]}amino-4-azaoctane | 868836-13-9

• 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: 1-amino-4-{N-[2,4,6-(trimethyl)benzenesulfonyl]}-8-{N-[4-(tert-butyl)benzyl]-N-[2,4,6-(trimethyl)benzenesulfonyl]}amino-4-azaoctane
• 英文别名: N-(3-aminopropyl)-N-[4-[(4-tert-butylphenyl)methyl-(2,4,6-trimethylphenyl)sulfonylamino]butyl]-2,4,6-trimethylbenzenesulfonamide
• CAS: 868836-13-9
• 化学式: C₃₆H₅₃N₃O₄S₂
• 分子量: 655.967
• InChiKey: JBBYYTVLFMAYKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-amino-4-{N-[2,4,6-(trimethyl)benzenesulfonyl]}-8-{N-[4-(tert-butyl)benzyl]-N-[2,4,6-(trimethyl)benzenesulfonyl]}amino-4-azaoctane 在 lithium hydroxide 、 氢溴酸 、 氯甲酸乙酯 、 溶剂黄146 、 三乙胺 、 苯酚 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 15.83h， 生成 17-N-[(4-tert-butyl)benzyl]amino-8-oxo-7,11-diazaheptadecanohydroxamic acid dihydrobromide
  参考文献：
  名称：

  Alkyl-Substituted Polyaminohydroxamic Acids:  A Novel Class of Targeted Histone Deacetylase Inhibitors

  摘要：

  The reversible acetylation of histones is critical for regulation of eukaryotic gene expression. The histone deacetylase inhibitors trichostatin (TSA, 1), MS-275 (2) and suberoylanilide, hydroxamic acid (SAHA, 3) arrest growth in transformed cells and in human tumor xenografts. However, 1-3 suffer from lack of specificity among the various HDAC isoforms, prompting us to design and synthesize polyaminohydroxamic acid (PAHA) derivatives 6-21. We felt that PAHAs would be selectively directed to chromatin and associated histones by the positively charged polyamine side chain. At 1 mu M, compounds 12, 15 and 20 inhibited HDAC by 74.86, 59.99 and 73.85%, respectively. Although 20 was a less potent HDAC inhibitor than 1, it was more potent than 2, more effective as an initiator of histone hyperacetylation, and significantly more effective than 2 at re-expressing p21(Waf1) in ML-1 leukemia cells. On the basis of these results, PAHAs 6-21 represent an important new chemical class of HDAC inhibitors.

  DOI：

  10.1021/jm0505009
• 作为产物：
  描述：

  4-叔丁基苄溴 在 sodium hydride 、 肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 1-amino-4-{N-[2,4,6-(trimethyl)benzenesulfonyl]}-8-{N-[4-(tert-butyl)benzyl]-N-[2,4,6-(trimethyl)benzenesulfonyl]}amino-4-azaoctane
  参考文献：
  名称：

  Alkyl-Substituted Polyaminohydroxamic Acids:  A Novel Class of Targeted Histone Deacetylase Inhibitors

  摘要：

  The reversible acetylation of histones is critical for regulation of eukaryotic gene expression. The histone deacetylase inhibitors trichostatin (TSA, 1), MS-275 (2) and suberoylanilide, hydroxamic acid (SAHA, 3) arrest growth in transformed cells and in human tumor xenografts. However, 1-3 suffer from lack of specificity among the various HDAC isoforms, prompting us to design and synthesize polyaminohydroxamic acid (PAHA) derivatives 6-21. We felt that PAHAs would be selectively directed to chromatin and associated histones by the positively charged polyamine side chain. At 1 mu M, compounds 12, 15 and 20 inhibited HDAC by 74.86, 59.99 and 73.85%, respectively. Although 20 was a less potent HDAC inhibitor than 1, it was more potent than 2, more effective as an initiator of histone hyperacetylation, and significantly more effective than 2 at re-expressing p21(Waf1) in ML-1 leukemia cells. On the basis of these results, PAHAs 6-21 represent an important new chemical class of HDAC inhibitors.

  DOI：

  10.1021/jm0505009