benzyl 6-(1,3-dioxoisoindolin-2-yloxy)hexanoate | 1418032-61-7

• 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: benzyl 6-(1,3-dioxoisoindolin-2-yloxy)hexanoate
• 英文别名: Benzyl 6-(1,3-dioxoisoindol-2-yl)oxyhexanoate；benzyl 6-(1,3-dioxoisoindol-2-yl)oxyhexanoate
• CAS: 1418032-61-7
• 化学式: C₂₁H₂₁NO₅
• 分子量: 367.401
• InChiKey: OWIAOPHUHCYSNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 6-(1,3-dioxoisoindolin-2-yloxy)hexanoate 在 吡啶 、 4-二甲氨基吡啶 、 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 1,2-二氯乙烷 、 甲基肼 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， -10.0~20.0 ℃ 、100.0 kPa 条件下， 反应 48.0h， 生成 N-((6-((benzyloxy)amino)-6-oxohexyl)oxy)-3-methylbenzamide
  参考文献：
  名称：

  Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC5 with Improved Activity against Chemoresistant Cancer Cells

  摘要：

  The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological evaluation includes MTT and cellular HDAC assays on sensitive and chemoresistant cancer cell lines as well as HDAC profiling of selected compounds. Compound 191 (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. Subsequent HDAC profiling yielded a novel HDAC isoform selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA). 19i shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range.

  DOI：

  10.1021/jm301254q
• 作为产物：
  描述：

  N-羟基邻苯二甲酰亚胺 、 6-溴己酸苄酯 在 三乙胺 作用下， 以 乙腈 为溶剂， 以74%的产率得到benzyl 6-(1,3-dioxoisoindolin-2-yloxy)hexanoate
  参考文献：
  名称：

  Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC5 with Improved Activity against Chemoresistant Cancer Cells

  摘要：

  The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological evaluation includes MTT and cellular HDAC assays on sensitive and chemoresistant cancer cell lines as well as HDAC profiling of selected compounds. Compound 191 (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. Subsequent HDAC profiling yielded a novel HDAC isoform selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA). 19i shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range.

  DOI：

  10.1021/jm301254q

文献信息

• Histone Deacetylase (HDAC) Inhibitors with a Novel Connecting Unit Linker Region Reveal a Selectivity Profile for HDAC4 and HDAC5 with Improved Activity against Chemoresistant Cancer Cells
  作者：Linda Marek、Alexandra Hamacher、Finn K. Hansen、Krystina Kuna、Holger Gohlke、Matthias U. Kassack、Thomas Kurz

  DOI：10.1021/jm301254q

  日期：2013.1.24

  The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological evaluation includes MTT and cellular HDAC assays on sensitive and chemoresistant cancer cell lines as well as HDAC profiling of selected compounds. Compound 191 (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat on inhibition of cellular HDACs in a pan-HDAC assay but enhanced cytotoxic effects against the human cancer cell lines A2780, Cal27, Kyse510, and MDA-MB231. Subsequent HDAC profiling yielded a novel HDAC isoform selectivity profile of 19i in comparison to vorinostat or trichostatin A (TSA). 19i shows nanomolar inhibition of HDAC4 and HDAC5, whereas vorinostat and TSA inhibit HDAC4 and HDAC5 in the higher micromolar range.