(2E)-2-hydroxyimino-N-[2-[2-[[(2E)-2-hydroxyimino-3-(5-iodo-1H-indol-3-yl)propanoyl]amino]ethyldisulfanyl]ethyl]-3-(5-iodo-1H-indol-3-yl)propanamide | 1403228-51-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2E)-2-hydroxyimino-N-[2-[2-[[(2E)-2-hydroxyimino-3-(5-iodo-1H-indol-3-yl)propanoyl]amino]ethyldisulfanyl]ethyl]-3-(5-iodo-1H-indol-3-yl)propanamide
• CAS: 1403228-51-2
• 化学式: C₂₆H₂₆I₂N₆O₄S₂
• 分子量: 804.471
• InChiKey: SWFUNRDUIVICJZ-IENBMRAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  206
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2E,2'E)-N,N'-[2,2'-disulfanediylbis(ethane-2,1-diyl)]bis[3-(5-iodo-1H-indol-3-yl)-2-(trityloxyimino)propanamide] 在 盐酸 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.0h， 以0.05 g的产率得到(2E)-2-hydroxyimino-N-[2-[2-[[(2E)-2-hydroxyimino-3-(5-iodo-1H-indol-3-yl)propanoyl]amino]ethyldisulfanyl]ethyl]-3-(5-iodo-1H-indol-3-yl)propanamide
  参考文献：
  名称：

  Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities

  摘要：

  A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the beta-indole-alpha-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD(+)-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders.

  DOI：

  10.1021/jm300618u

文献信息

• Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities
  作者：Raquel Pereira、Rosaria Benedetti、Santiago Pérez-Rodríguez、Angela Nebbioso、José García-Rodríguez、Vincenzo Carafa、Mayra Stuhldreier、Mariarosaria Conte、Fátima Rodríguez-Barrios、Hendrik G. Stunnenberg、Hinrich Gronemeyer、Lucia Altucci、Ángel R. de Lera

  DOI：10.1021/jm300618u

  日期：2012.11.26

  A SAR study has been carried out around a modified scaffold of the natural product psammaplin A obtained by replacing the o-bromophenol unit by an indole ring. A series of indole psammaplin A constructs were generated in a short synthetic sequence that starts with the functionalization of the C3 indole position with in situ generated nitrosoacrylate, and this is followed by protection of the beta-indole-alpha-oximinoesters, saponification, condensation with symmetrical diamines, and deprotection. Biochemical and cellular characterization using U937 and MCF-7 cells confirmed that many of these analogues displayed more potent actitivies than the parent natural product. Moreover, in addition to the reported HDAC and DNMT dual epigenetic inhibitory profile of the parent compound, some analogues, notably 4a (UVI5008), also inhibited the NAD(+)-dependent SIRT deacetylase enzymes. The SAR study provides structural insights into the mechanism of action of these multiple epigenetic ligands and paves the way for additional structural exploration to optimize their pharmacological profiles. Because of their multi(epi)target features and their action in ex vivo samples, the indole-based psammaplin A derivatives are attractive molecules for the modulation of epigenetic disorders.