2-benzylisoindolin-1,3-dione-5-carboxylic acid chloride | 67822-79-1

• 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-benzylisoindolin-1,3-dione-5-carboxylic acid chloride
• 英文别名: 2-Benzyl-1,3-dioxoisoindole-5-carbonyl chloride
• CAS: 67822-79-1
• 化学式: C₁₆H₁₀ClNO₃
• 分子量: 299.713
• InChiKey: YRNXJULVCLKKFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-benzylisoindolin-1,3-dione-5-carboxylic acid chloride 在 palladium on activated charcoal copper(l) iodide 、 高氯酸 、 氢气 作用下， 以 溶剂黄146 为溶剂， -40.0~25.0 ℃ 、241.32 kPa 条件下， 反应 2.33h， 生成 2-Benzyl-5-ethyl-isoindole-1,3-dione
  参考文献：
  名称：

  Synthesis of isotopically-labelled nitroxyl radicals for use as spin probes

  摘要：

  [15N]-1,1,3,3-四（三氘代甲基）异吲哚啉-2-基氧基和一些 5-烷基衍生物的合成已通过标准合成路线实现。1 氘的存在提高了信号的清晰度，这与氮 15 的掺入一起增强了此类化合物作为自旋探针的应用； C-5处的烷基取代基提高了亲脂性。

  DOI：

  10.1002/jlcr.2580340711
• 作为产物：
  描述：

  2-Benzyl-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylic acid benzylamide 在 盐酸 、 氯化亚砜 作用下， 以 溶剂黄146 为溶剂， 反应 2.17h， 生成 2-benzylisoindolin-1,3-dione-5-carboxylic acid chloride
  参考文献：
  名称：

  Synthesis of isotopically-labelled nitroxyl radicals for use as spin probes

  摘要：

  [15N]-1,1,3,3-四（三氘代甲基）异吲哚啉-2-基氧基和一些 5-烷基衍生物的合成已通过标准合成路线实现。1 氘的存在提高了信号的清晰度，这与氮 15 的掺入一起增强了此类化合物作为自旋探针的应用； C-5处的烷基取代基提高了亲脂性。

  DOI：

  10.1002/jlcr.2580340711

文献信息

• Design, Synthesis, and Evaluation of Isoindoline Derivatives as New Antidepressant Agents
  作者：Ai-Ling Sun、Chao-Chao Wang、Hao Zhou、Yi-Fei Lang、Shu-Yue Fu、Ren-Min Liu、Kang Lei

  DOI：10.2174/1570180819666220301141149

  日期：2022.8

  Isoindoline derivatives exhibit a wide range of biological activities and have attracted considerable attention. However, few studies have been conducted on their antidepressant activity.

  Here, we designed and synthesized a series of isoindoline derivatives and studied their antidepressant activities.

  Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant activity of the target compounds. The most active compound was used to evaluate the exploratory activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate if the compound has an effect on the mice brain by using ELISA. The biological activities of the compounds were verified by molecular docking studies. The pharmacokinetic properties of the target compounds were predicted by Discovery Studio (DS) 2020.

  The results of the pharmacological experiments showed that most isoindoline derivatives exhibited significant antidepressant activity. Among these compounds, compound 4j showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of isoindoline derivatives may be mediated by elevated 5-HT levels. Compound 4j was used in molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT1A receptor. The results demonstrated that compound 4j had a significant interaction with amino acids around the active site of the 5-HT1A receptor in the homology model.

  Isoindoline derivatives synthesized in this study have a significant antidepressant activity. These findings can be useful in the design and synthesis of novel antidepressants.

  背景： 异吲哚啉衍生物展示了广泛的生物活性，并且引起了相当大的关注。然而，对它们的抗抑郁活性进行的研究很少。 目的： 在这里，我们设计并合成了一系列的异吲哚啉衍生物，并研究了它们的抗抑郁活性。 方法： 强迫游泳试验（FST）和尾悬试验（TST）被用来评估目标化合物的抗抑郁活性。最活跃的化合物被用来通过开放场测试评估动物的探索活动。使用ELISA评估5-HT浓度来评估化合物是否对小鼠大脑产生影响。通过分子对接研究验证化合物的生物活性。通过Discovery STudio（DS）2020预测目标化合物的药代动力学特性。 结果： 药理实验的结果表明，大多数异吲哚啉衍生物表现出显著的抗抑郁活性。在这些化合物中，化合物4j表现出最高的抗抑郁活性。小鼠脑中5-HT水平的测量结果表明，异吲哚啉衍生物的抗抑郁活性可能是通过升高5-HT水平介导的。化合物4j被用于分子对接实验，模拟这些化合物与5-HT1A受体的可能相互作用。结果表明，化合物4j与5-HT1A受体同源模型中活性位点周围的氨基酸有显著的相互作用。 结论： 本研究合成的异吲哚啉衍生物具有显著的抗抑郁活性。这些发现对设计和合成新型抗抑郁药物有用。
• Design, synthesis, and biological evaluation of 1,3-dioxoisoindoline-5-carboxamide derivatives as T-type calcium channel blockers
  作者：Hwa Sil Kim、Yoonjee Kim、Munikumar Reddy Doddareddy、Seon Hee Seo、Hyewhon Rhim、Jinsung Tae、Ae Nim Pae、Hyunah Choo、Yong Seo Cho

  DOI：10.1016/j.bmcl.2006.10.042

  日期：2007.1

  A small molecule library of 1,3-dioxoisoindoline-5-carboxamides 4 was designed based on the pharmacophore model, synthesized and biologically evaluated as potential T-type calcium channel blockers. The most active compounds 4d and 4n show T-type calcium channel blocking activity with IC50 values of 0.93 and 0.96 mu M, respectively. (c) 2006 Elsevier Ltd. All rights reserved.