2-(2,6-dioxo-3-piperidyl)-4-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione | 1216805-67-2

• 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: 2-(2,6-dioxo-3-piperidyl)-4-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione
• 英文别名: (RS)-2-(2,6-dioxopiperidin-3-yl)-4-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione；Thalidomide-propargyl-OH；2-(2,6-dioxopiperidin-3-yl)-4-(3-hydroxyprop-1-ynyl)isoindole-1,3-dione
• CAS: 1216805-67-2
• 化学式: C₁₆H₁₂N₂O₅
• 分子量: 312.282
• InChiKey: PDVQCRGWUAGFKJ-UHFFFAOYSA-N

物化性质

• 熔点：
  214-217 °C
• 沸点：
  621.8±55.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2,6-dioxo-3-piperidyl)-4-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione 在 palladium 10% on activated carbon 、 氢气 、 palladium(II) hydroxide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 20.0 ℃ 、103.42 kPa 条件下， 反应 6.0h， 生成 3-[2-(2,6-dioxo-3-piperidyl)-1,3-dioxoisoindolin-4-yl]propyl methanesulfonate
  参考文献：
  名称：

  IRAK DEGRADERS AND USES THEREOF

  摘要：

  本发明提供了化合物、其组合物以及使用这些化合物的方法。

  公开号：

  US20190192668A1
• 作为产物：
  描述：

  2-(2,6-dioxopiperidin-3-yl)-4-iodoisoindoline-1,3-dione 、 2-丙炔-1-醇 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 以78%的产率得到2-(2,6-dioxo-3-piperidyl)-4-(3-hydroxyprop-1-ynyl)isoindoline-1,3-dione
  参考文献：
  名称：

  New thalidomide analogues derived through Sonogashira or Suzuki reactions and their TNF expression inhibition profiles

  摘要：

  A library of new thalidomide C4/5 analogues containing either a phenyl or alkyne tether were synthesized using Sonogashira or Suzuki cross coupling reactions from their aryl halogenated precursors. All thalidomide analogues were tested for their ability to inhibit the expression of the proinflammatory cytokine Tumor Necrosis Factor (TNF). More explicitly the use of a novel reporter system utilizing the promoter region of the TNF gene in a human T-cell line provided a rapid and effective measure of NF kappa B transcriptional activity. Several compounds either containing either an aryl-isobutyl or aryl-isopropoxy group were the most effective in inhibiting TNF expression, and were several times more active than thalidomide itself. Five of the more active derivatives indicated an apoptotic response while one of these compounds, containing an aldehyde tether, showed possible influence of cell cycling effects. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.001

文献信息

• IRAK degraders and uses thereof
  申请人：Kymera Therapeutics, Inc.

  公开号：US10874743B2

  公开（公告）日：2020-12-29

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用方法。
• Identification of a thalidomide derivative that selectively targets tumorigenic liver progenitor cells and comparing its effects with lenalidomide and sorafenib
  作者：Ken Woo、Scott G. Stewart、Geraldine S. Kong、Megan L. Finch-Edmondson、Benjamin J. Dwyer、Sing Y. Yeung、Lawrence J. Abraham、Sven S. Kampmann、Luke A. Diepeveen、Adam M. Passman、Caryn L. Elsegood、Janina E.E. Tirnitz-Parker、Bernard A. Callus、John K. Olynyk、George C.T. Yeoh

  DOI：10.1016/j.ejmech.2016.03.015

  日期：2016.9

  Background & aims: The availability of non-tumorigenic and tumorigenic liver progenitor cell (LPC) lines affords a method to screen putative anti-liver cancer agents to identify those that are selectively effective. To prove this principle we tested thalidomide and a range of its derivatives and compared them to lenalidomide and sorafenib, to assess their growth-inhibitory effects.Methods: Cell growth, the mitotic and apoptotic index of cell cultures were measured using the Cellavista instrument (SynenTec) using commercially available reagents.Results: Neither lenalidomide nor thalidomide (100 mu M) affected tumorigenic LPCs but killed their non-tumorigenic counterparts. Sorafenib arrested growth in both cell types. All but two derivatives of thalidomide were ineffective; of the two effective derivatives, one (thalidomide Cl) specifically affected the tumorigenic cell line (10 mu M). Mitotic and apoptotic analyses revealed that thalidomide Cl induced apoptotic cell death and not mitotic arrest.Conclusions: This study shows that screens incorporating non-tumorigenic and tumorigenic liver cell lines are a sound approach to identify agents that are effective and selective. A high throughput instrument such as the Cellavista affords robust and reproducible objective measurements with a large number of replicates that are reliable. These experiments show that neither lenalidomide nor thalidomide are potentially useful for anti-liver cancer therapy as they kill non-tumorigenic liver cells and not their tumorigenic counterparts. Sorafenib in contrast, is highly effective, but not selective. One tested thalidomide derivative has potential as an anti-tumor drug since it induced growth arrest; and importantly, it selectively induced apoptotic cell death only in tumorigenic liver progenitor cells. (C) 2016 Elsevier Masson SAS. All rights reserved.
• IRAK DEGRADERS AND USES THEREOF
  申请人：Kymera Therapeutics, Inc.

  公开号：US20190192668A1

  公开（公告）日：2019-06-27

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用这些化合物的方法。
• New thalidomide analogues derived through Sonogashira or Suzuki reactions and their TNF expression inhibition profiles
  作者：Scott G. Stewart、Carlos J. Braun、Sze-Ling Ng、Marta E. Polomska、Mahdad Karimi、Lawrence J. Abraham

  DOI：10.1016/j.bmc.2009.12.001

  日期：2010.1

  A library of new thalidomide C4/5 analogues containing either a phenyl or alkyne tether were synthesized using Sonogashira or Suzuki cross coupling reactions from their aryl halogenated precursors. All thalidomide analogues were tested for their ability to inhibit the expression of the proinflammatory cytokine Tumor Necrosis Factor (TNF). More explicitly the use of a novel reporter system utilizing the promoter region of the TNF gene in a human T-cell line provided a rapid and effective measure of NF kappa B transcriptional activity. Several compounds either containing either an aryl-isobutyl or aryl-isopropoxy group were the most effective in inhibiting TNF expression, and were several times more active than thalidomide itself. Five of the more active derivatives indicated an apoptotic response while one of these compounds, containing an aldehyde tether, showed possible influence of cell cycling effects. (C) 2009 Elsevier Ltd. All rights reserved.