7-{4-[(phthalimido)amino]butyl}-{N-[4-N,N-(dimethyl)aminobenzyl]carbamoyl}heptanoic acid methyl ester | 868836-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 7-{4-[(phthalimido)amino]butyl}-{N-[4-N,N-(dimethyl)aminobenzyl]carbamoyl}heptanoic acid methyl ester
• 英文别名: 7-{4-[(phthalimido)amino]butyl}-{N-[4-N,N-(dimethyl)-aminobenzyl]carbamoyl}heptanoic acid methyl ester；Methyl 8-[[4-(dimethylamino)phenyl]methyl-[4-(1,3-dioxoisoindol-2-yl)butyl]amino]-8-oxooctanoate
• CAS: 868836-41-3
• 化学式: C₃₀H₃₉N₃O₅
• 分子量: 521.657
• InChiKey: FYVIEAZGQCSDAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  87.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-{4-[(phthalimido)amino]butyl}-{N-[4-N,N-(dimethyl)aminobenzyl]carbamoyl}heptanoic acid methyl ester 在 lithium hydroxide 、 氯甲酸乙酯 、 碳酸氢钠 、 三乙胺 、 sodium chloride 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 14.83h， 生成 7-{[4-(amino)butyl]-N-[4-(dimethylaminobenzyl)-carbamoyl]}heptano-hydroxamic acid trifluoroacetate
  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：

  N-(4-azidobutyl)phthalimide 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 24.33h， 生成 7-{4-[(phthalimido)amino]butyl}-{N-[4-N,N-(dimethyl)aminobenzyl]carbamoyl}heptanoic acid methyl ester
  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

• Histone deacetylase inhibitors
  申请人：Casero Robert A.

  公开号：US20090182019A1

  公开（公告）日：2009-07-16

  The present invention provides novel HDAC inhibitors and methods of treating diseases using the same.

  本发明提供了新型HDAC抑制剂和使用其治疗疾病的方法。
• [EN] HISTONE DEACETYLASE INHIBITORS<br/>[FR] INHIBITEURS DE L'HISTONE DESACETYLASE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2006113606A2

  公开（公告）日：2006-10-26

  [EN] The present invention provides novel HDAC inhibitors and methods of treating diseases using the same.
  [FR] La présente invention concerne de nouveaux inhibiteurs de la HDAC ainsi que des méthodes destinées à traiter des maladies au moyen de ceux-ci.