(2E,2′E)-N,N′-[2,2′-disulfanediylbis(ethane-2,1-diyl)]bis[3-(5-bromo-1H-indol-3-yl)-2-(trityloxyimino)propanamide] | 1071822-51-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2E,2′E)-N,N′-[2,2′-disulfanediylbis(ethane-2,1-diyl)]bis[3-(5-bromo-1H-indol-3-yl)-2-(trityloxyimino)propanamide]
• 英文别名: UVI5018
• CAS: 1071822-51-9
• 化学式: C₆₄H₅₄Br₂N₆O₄S₂
• 分子量: 1195.11
• InChiKey: KJEZKJDIRCYEKU-SFKSMFNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.3
• 重原子数：
  78.0
• 可旋转键数：
  23.0
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  132.96
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (2E,2′E)-N,N′-[2,2′-disulfanediylbis(ethane-2,1-diyl)]bis[3-(5-bromo-1H-indol-3-yl)-2-(trityloxyimino)propanamide] 在 盐酸 、 sodium tetrahydroborate 、 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 (2E)-3-(5-bromo-1H-indol-3-yl)-2-hydroxyimino-N-(2-sulfanylethyl)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
• 作为产物：
  描述：

  胱胺 、 在 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 15.0h， 生成 (2E,2′E)-N,N′-[2,2′-disulfanediylbis(ethane-2,1-diyl)]bis[3-(5-bromo-1H-indol-3-yl)-2-(trityloxyimino)propanamide]
  参考文献：
  名称：

  Derivatives of psammaplin A, a method for their synthesis and their use for the prevention or treatment of cancer

  摘要：

  桑普林A的衍生物，其化学公式为(I)，一种用于合成它们的方法，以及它们用于制备用于预防肿瘤或癌症的药物。

  公开号：

  EP1964835A1