7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanoic acid | 868836-04-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanoic acid
• 英文别名: 8-[4-[(4-Methylphenyl)methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butylamino]-8-oxooctanoic acid
• CAS: 868836-04-8
• 化学式: C₂₅H₄₀N₂O₅
• 分子量: 448.603
• InChiKey: BPMKCNIQZSJNKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanoic acid 在 氯甲酸乙酯 、 三乙胺 、 羟胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.83h， 以78%的产率得到7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanohydroxamic acid
  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：

  7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanoic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以72.7%的产率得到7-{4-[(tert-butyloxy)carbonyl]-[4-(methyl)benzyl]amino}butylcarbamoylheptanoic acid
  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

文献信息

• Alkyl-Substituted Polyaminohydroxamic Acids:  A Novel Class of Targeted Histone Deacetylase Inhibitors
  作者：Sheeba Varghese、Deepak Gupta、Tiffany Baran、Anchalee Jiemjit、Steven D. Gore、Robert A. Casero,、Patrick M. Woster

  DOI：10.1021/jm0505009

  日期：2005.10.1

  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.