5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)benzyl]amino}butylcarbamoylpentanohydroxamic acid | 868836-08-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)benzyl]amino}butylcarbamoylpentanohydroxamic acid
• 英文别名: 5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)-benzyl]amino}butylcarbamoyl-pentanohydroxamic acid；tert-butyl N-[[4-(dimethylamino)phenyl]methyl]-N-[4-[[6-(hydroxyamino)-6-oxohexanoyl]amino]butyl]carbamate
• CAS: 868836-08-2
• 化学式: C₂₄H₄₀N₄O₅
• 分子量: 464.605
• InChiKey: RSZMZTXNQNFVFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  33
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)benzyl]amino}butylcarbamoylpentanohydroxamic acid 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 8.0h， 以76.7%的产率得到5-{4-[4-N,N-(dimethyl)aminobenzyl]amino}butylcarbamoylpentanohydroxamic acid trifluoroacetate
  参考文献：
  名称：

  WO2006/113606

  摘要：

  公开号：
• 作为产物：
  描述：

  5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)benzyl]amino}butylcarbamoylpentanoic acid 在 羟胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.83h， 生成 5-{4-[N-(tert-butyloxy)carbonyl]-4-[N,N-(dimethylamino)benzyl]amino}butylcarbamoylpentanohydroxamic acid
  参考文献：
  名称：

  WO2006/113606

  摘要：

  公开号：

文献信息

• WO2006/113606
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.