3-(2,4-dichlorophenyl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione | 1265131-70-1

• 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: 3-(2,4-dichlorophenyl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
• 英文别名: 3-(2,4-dichlorophenyl)-4-(1H-indol-3-yl)pyrrole-2,5-dione
• CAS: 1265131-70-1
• 化学式: C₁₈H₁₀Cl₂N₂O₂
• 分子量: 357.196
• InChiKey: LQYUVXKQUPVRKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2,4-dichlorophenyl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione 在 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 3-(2,4-dichlorophenyl)-1-(2,4-dimethoxybenzyl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  Synthesis and Initial in Vivo Studies with [¹¹C]SB-216763: The First Radiolabeled Brain Penetrative Inhibitor of GSK-3

  摘要：

  Quantifying glycogen synthase kinase-3 (GSK-3) activity in vivo using positron emission tomography (PET) imaging is of interest because dysregulation of GSK-3 is implicated in numerous diseases and neurological disorders for which GSK-3 inhibitors are being considered as therapeutic strategies. Previous PET radiotracers for GSK-3 have been reported, but none of the published examples cross the blood-brain barrier. Therefore, we have an ongoing interest in developing a brain penetrating radiotracer for GSK-3. To this end, we were interested in synthesis and preclinical evaluation of [C-11]SB-216763, a high-affinity inhibitor of GSK-3 (K-i = 9 nM; IC50 = 34 nM). Initial radiosyntheses of [C-11]SB-216763 proved ineffective in our hands because of competing [3 + 3] sigmatropic shifts. Therefore, we have developed a novel one-pot two-step synthesis of [C-11]SB-216763 from a 2,4-dimethoxybenzyl-protected maleimide precursor, which provided high specific activity [C-11]SB-216763 in 1% noncorrected radiochemical yield (based upon [C-11]CH3I) and 97-100% radiochemical purity (n = 7). Initial preclinical evaluation in rodent and nonhuman primate PET imaging studies revealed high initial brain uptake (peak rodent SUV = 2.5 @ 3 min postinjection; peak nonhuman primate SUV = 1.9 @ 5 min postinjection) followed by washout. Brain uptake was highest in thalamus, striatum, cortex, and cerebellum, areas known to be rich in GSK-3. These results make the arylindolemaleimide skeleton our lead scaffold for developing a PET radiotracer for quantification of GSK-3 density in vivo and ultimately translating it into clinical use.

  DOI：

  10.1021/acsmedchemlett.5b00044
• 作为产物：
  描述：

  吲哚-3-乙醛酸甲酯 、 2,4-二氯-苯乙酰胺 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以71%的产率得到3-(2,4-dichlorophenyl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  The first synthesis of [11C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3)

  摘要：

  SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC50 value of 34 nM. [C-11]SB-216763 (3-(2,4-dichlorophenyl)-4-(1-[C-11]methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay corrected radiochemical yield and 370-555 GBq/mu mol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.026

文献信息

• [EN] COMPOSITIONS AND METHODS FOR IDENTIFYING LATENTLY INFECTED CELLS<br/>[FR] COMPOSITIONS ET PROCÉDÉS PERMETTANT D'IDENTIFIER DES CELLULES INFECTÉES DE MANIÈRE LATENTE.
  申请人：DAVID GLADSTONE INST

  公开号：WO2015023811A2

  公开（公告）日：2015-02-19

  The present disclosure provides for recombinant nucleic acids, and cells and virions comprising the recombinant nucleic acids, that can be used to identify, isolate, and/or purify cells latently infected with immunodeficiency virus. A subject recombinant nucleic acid includes (a) a first nucleotide sequence encoding a first reporter polypeptide that produces a first detectable signal, where the first nucleotide sequence is operably linked to an immunodeficiency virus promoter and is translated as an early gene; and (b) a second nucleotide sequence encoding a second reporter polypeptide that produces a second detectable signal that is distinguishable from the first detectable signal, where the second nucleotide sequence is operably linked to a non-immunodeficiency virus promoter. In some aspects, the first and second nucleotide sequences are both positioned between a shared 5' long terminal repeat (LTR) and a shared 3' LTR. Also provided are related methods.