1,3-Dioxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid | 166096-57-7

• 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: 1,3-Dioxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid
• 英文别名: 1,3-dioxo-2-(2-phenylethyl)isoindole-5-carboxylic acid
• CAS: 166096-57-7
• 化学式: C₁₇H₁₃NO₄
• mdl: MFCD02905255
• 分子量: 295.295
• InChiKey: ICDZUDIRGRAYIV-UHFFFAOYSA-N

物化性质

• 溶解度：
  >44.3 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.117
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,3-Dioxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid 在 2-氯-1-甲基吡啶碘化物 、 三乙胺 、 丙酮氰醇 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  吡唑-异吲哚啉-1,3-二酮杂化物：4-羟基苯丙酮酸双加氧酶抑制剂的有前途的支架

  摘要：

  4-羟基苯基丙酮酸双加氧酶（HPPD，EC 1.13.11.27）抑制剂的发现由于其作为除草剂除草剂的巨大潜力而​​成为一个活跃的研究领域。从已知的HPPD抑制剂的结合模式出发，通过将2-苯并lethen-1-ol和isoindoline-1,3-dione片段杂交，设计并合成了一系列具有新分子支架的HPPD抑制剂。的体外试验的结果表明，新合成的化合物显示出良好的HPPD抑制活性IC 50个针对重组值拟南芥HPPD（在HPPD）范围为0.0039μM到超过1微米。最有希望的是化合物4ae，2-苄基-5-（5-羟基-1,3-二甲基-1 H吡唑-4-羰基）异二氢吲哚-1,3-二酮，显示出最高的在与HPPD抑制活性ķ我3.92纳米的值，使得它大约10倍，比磺酰草吡唑更有效（ķ我= 44 nM）的和稍微更比甲基磺草酮有效（K i = 4.56 nM）。此外，At HPPD– 4ae的共晶体结构该复合物已成功解析为1

  DOI：

  10.1021/acs.jafc.9b04917
• 作为产物：
  描述：

  2-苯乙胺 、 偏苯三酸酐 在 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 1,3-Dioxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid
  参考文献：
  名称：

  异二氢吲哚衍生物作为新型抗抑郁药的设计、合成和评价

  摘要：

  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。

  DOI：

  10.2174/1570180819666220301141149

文献信息

• Synthesis and anti-inflammatory activity of sulfonamides and carboxylates incorporating trimellitimides: Dual cyclooxygenase/carbonic anhydrase inhibitory actions
  作者：Alaa A.-M. Abdel-Aziz、Andrea Angeli、Adel S. El-Azab、Mohammed E.A. Hammouda、Magda A. El-Sherbeny、Claudiu T. Supuran

  DOI：10.1016/j.bioorg.2018.11.033

  日期：2019.3

  Trimellitimides 6-21 were prepared and investigated in vivo for anti-inflammatory and ulcerogenic effects and in vitro for cytotoxicity. They were subjected to in vitro cyclooxygenase (COX-1/2) and carbonic anhydrase inhibition protocols. Compounds 6-11 and 18 exhibited anti-inflammatory activities and had median effective doses (ED50) of 34.3-49.8 mg kg(-1) and 63.6-86.6% edema inhibition relative to the reference drug celecoxib (ED50 : 33.9 mg kg(-1) and 85.2% edema inhibition). Compounds 6-11 and 18 were weakly cytotoxic at 10 mu M against 59 cell lines compared with the reference standard 5-fluorouracil (5-FU). Compounds 6-11 had optimal selectivity against COX-2. The selectivity index (SI) range was > 200-490 and was comparable to that for celecoxib [COX-2 (SI) > 416.7]. In contrast, compounds 12, 13, and 16-18 were nonselective COX inhibitors with a selectivity index range of 0.92-0.25. The carbonic anhydrase inhibition assay showed that sulfonamide incorporating trimellitimides 6-11 inhibited the cytosolic isoforms hCA I and hCA II, and tumor-associated isoform hCA IX. They were relatively more susceptible to inhibition by compounds 8, 9, and 11. The K-1 ranges were 54.1-81.9 nM for hCA I, 25.9-55.1 nM for hCA II, and 46.0-348.3 nM for hCA IX. (C) 2018 Elsevier Science. All rights reserved.
• Design and synthesis of phthalimide-type histone deacetylase inhibitors
  作者：Chihiro Shinji、Takanori Nakamura、Satoko Maeda、Minoru Yoshida、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmcl.2005.07.048

  日期：2005.10

  Several hydroxamic acid derivatives with a substituted phthalimicle group as a linker and/or cap structure, prepared during structural development studies based on thalidomide, were found to have historic deacetylase (HDAC)-inhibitory activity. Structure-activity relationship studies indicated that nature of the substituent introduced at the phthalimide nitrogen atom, introduction of a hydroxamic acid structure, and distance between the N-hydroxyl group and the cap structure are important for HDAC-inhibitory activity. (c) 2005 Elsevier Ltd. All rights reserved.
• Pyrazole–Isoindoline-1,3-dione Hybrid: A Promising Scaffold for 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors
  作者：Bo He、Jin Dong、Hong-Yan Lin、Meng-Yao Wang、Xian-Kai Li、Bai-Feng Zheng、Qiong Chen、Ge-Fei Hao、Wen-Chao Yang、Guang-Fu Yang

  DOI：10.1021/acs.jafc.9b04917

  日期：2019.10.2

  The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The

  4-羟基苯基丙酮酸双加氧酶（HPPD，EC 1.13.11.27）抑制剂的发现由于其作为除草剂除草剂的巨大潜力而​​成为一个活跃的研究领域。从已知的HPPD抑制剂的结合模式出发，通过将2-苯并lethen-1-ol和isoindoline-1,3-dione片段杂交，设计并合成了一系列具有新分子支架的HPPD抑制剂。的体外试验的结果表明，新合成的化合物显示出良好的HPPD抑制活性IC 50个针对重组值拟南芥HPPD（在HPPD）范围为0.0039μM到超过1微米。最有希望的是化合物4ae，2-苄基-5-（5-羟基-1,3-二甲基-1 H吡唑-4-羰基）异二氢吲哚-1,3-二酮，显示出最高的在与HPPD抑制活性ķ我3.92纳米的值，使得它大约10倍，比磺酰草吡唑更有效（ķ我= 44 nM）的和稍微更比甲基磺草酮有效（K i = 4.56 nM）。此外，At HPPD– 4ae的共晶体结构该复合物已成功解析为1
• 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。