2-(2,6-dioxopiperidin-3-yl)-4-(p-tolylthio)isoindoline-1,3-dione

• 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-dioxopiperidin-3-yl)-4-(p-tolylthio)isoindoline-1,3-dione
• 英文别名: 2-(2,6-Dioxopiperidin-3-yl)-4-(4-methylphenyl)sulfanylisoindole-1,3-dione；2-(2,6-dioxopiperidin-3-yl)-4-(4-methylphenyl)sulfanylisoindole-1,3-dione
• 化学式: C₂₀H₁₆N₂O₄S
• 分子量: 380.424
• InChiKey: YLNDENNQIVBSIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,2-二甲基-3-碘苯 在 吡啶 、 potassium permanganate 、 [Pd₂(dba)₃]*CHCl₃ 、 三乙胺 、 N,N-二异丙基乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 118.0h， 生成 2-(2,6-dioxopiperidin-3-yl)-4-(p-tolylthio)isoindoline-1,3-dione
  参考文献：
  名称：

  In pursuit of a selective hepatocellular carcinoma therapeutic agent: Novel thalidomide derivatives with antiproliferative, antimigratory and STAT3 inhibitory properties

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113353

文献信息

• Design, synthesis and biological evaluation of thioether-containing lenalidomide and pomalidomide derivatives with anti-multiple myeloma activity
  作者：Yuhong Wang、Tian Mi、Yiming Li、Weijuan Kan、Gaoya Xu、Jingya Li、Yubo Zhou、Jia Li、Xuefeng Jiang

  DOI：10.1016/j.ejmech.2020.112912

  日期：2021.1

  Lenalidomide and its analogs are well-known for treating multiple myeloma. In this work, designed sulfide-modified lenalidomide and pomalidomide were synthesized and evaluated. The anti-proliferative activity against MM.1S cell line of 3ak (IC₅₀ = 79 nM) was similar to lenalidomide (IC₅₀ = 81 nM). Compared to benzylic thioether substituted lenalidomide 3a, the half-live (T_1/2) of 4-F-phenyl-thioether analogs 3ak in human liver microsomes was promoted from 3 min to 416.7 min. The corresponding metabolic factor of 3ak was increased from 2.8% to 79.5%, which was slightly lower than lenalidomide (91.5%). Moreover, the IKZF1 degradation of 3y and 3ak was well related with corresponding IC₅₀ values, which suggested the IKZF1 degradation efficiency is correlated to the responses of MM1. S cells. Furthermore, the oral administration of compounds 3y and 3ak at dosages of 60 mg/kg could delay tumor growth in female CB-17 SCID mice. This research helped to prompt the stability of thioether lenalidomide analogs, which paved the way for developing better molecules for treating multiple myeloma.
• In pursuit of a selective hepatocellular carcinoma therapeutic agent: Novel thalidomide derivatives with antiproliferative, antimigratory and STAT3 inhibitory properties
  作者：Michael J. Nutt、Yeung Sing Yee、Amanda Buyan、Neil Andrewartha、Ben Corry、George C.T. Yeoh、Scott G. Stewart

  DOI：10.1016/j.ejmech.2021.113353

  日期：2021.5