ethyl α-(hydroxyimino)-β-indol-3-ylpropanoate | 99708-03-9

• 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: ethyl α-(hydroxyimino)-β-indol-3-ylpropanoate
• 英文别名: (E)-ethyl 2-(hydroxyimino)-3-(1H-indol-3-yl)propanoate；ethyl 2-hydroxyimino-3-[1H-indol-3-yl]propanoate；ethyl (2E)-2-hydroxyimino-3-(1H-indol-3-yl)propanoate
• CAS: 99708-03-9
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: FHYUDILKXGAYJK-NTCAYCPXSA-N

物化性质

• 沸点：
  472.9±47.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  74.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl α-(hydroxyimino)-β-indol-3-ylpropanoate 在 盐酸 、 硼烷-三甲胺络合物 、 三氟乙酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 516.0h， 生成 β-咔啉-3-羧酸乙酯
  参考文献：
  名称：

  Nitrone cycloaddition in the stereoselective synthesis of .beta.-carbolines from N-hydroxytryptophan

  摘要：

  DOI：

  10.1021/jo00353a007
• 作为产物：
  描述：

  3-溴丙酮酸乙酯 在 盐酸羟胺 、 sodium carbonate 、 ethyl 2-nitrosopropenoate 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 42.0h， 生成 ethyl α-(hydroxyimino)-β-indol-3-ylpropanoate
  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

• Derivatives of psammaplin A, a method for their synthesis and their use for the prevention or treatment of cancer
  申请人：Centre National de la Recherche Scientifique

  公开号：EP1964835A1

  公开（公告）日：2008-09-03

  Derivatives of psammaplin A of formula (I), a method for their synthesis and their use for the preparation of a medicament for preventing and /or treating a tumor or a cancer.

  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。
• Nitrone cycloaddition in the stereoselective synthesis of .beta.-carbolines from N-hydroxytryptophan
  作者：Ralf Plate、Pedro H. H. Hermkens、Jan M. M. Smits、Harry C. J. Ottenheijm

  DOI：10.1021/jo00353a007

  日期：1986.2
• 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.