2-苄基-1,3-二氧代异吲哚啉-5-羧酸 | 67822-75-7

• 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
• 中文名称: 2-苄基-1,3-二氧代异吲哚啉-5-羧酸
• 英文名称: N-benzyl-1,3-dioxoisoindoline-5-carboxylic acid
• 英文别名: 2-benzylisoindolin-1,3-dione-5-carboxylic acid；2-Benzyl-1,3-dioxoisoindoline-5-carboxylic acid；2-benzyl-1,3-dioxoisoindole-5-carboxylic acid
• CAS: 67822-75-7
• 化学式: C₁₆H₁₁NO₄
• mdl: MFCD00411831
• 分子量: 281.268
• InChiKey: KGHOAEZOEVGKMU-UHFFFAOYSA-N

物化性质

• 熔点：
  198-201 °C
• 沸点：
  520.4±43.0 °C(Predicted)
• 密度：
  1.454±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.062
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2925190090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  2-苄基-1,3-二氧代异吲哚啉-5-羧酸 在 palladium on activated charcoal copper(l) iodide 、 氯化亚砜 、 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 4.33h， 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 作用下， 以 溶剂黄146 为溶剂， 反应 0.17h， 生成 2-苄基-1,3-二氧代异吲哚啉-5-羧酸
  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

• 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 cyclic amide/imide-bearing hydroxamic acid derivatives as class-selective histone deacetylase (HDAC) inhibitors
  作者：Chihiro Shinji、Satoko Maeda、Keisuke Imai、Minoru Yoshida、Yuichi Hashimoto、Hiroyuki Miyachi

  DOI：10.1016/j.bmc.2006.07.008

  日期：2006.11

  A series of hydroxamic acid derivatives bearing a cyclic amide/imide group as a linker and/or cap structure, prepared during our structural development studies based on thalidomide, showed class-selective potent histone deacetylase (HDAC)-inhibitory activity. Structure-activity relationship studies indicated that the steric character of the substituent introduced at the cyclic amide/imide nitrogen

  在我们根据沙利度胺进行的结构开发研究中制备的一系列带有环状酰胺/酰亚胺基团作为连接基和/或帽结构的异羟肟酸衍生物显示出对类组有效的组蛋白脱乙酰基酶（HDAC）的抑制活性。结构-活性关系研究表明，在环状酰胺/酰亚胺氮原子上引入的取代基的空间特征，酰胺/酰亚胺羰基的存在，异羟肟酸的结构，连接基团的形状以及它们之间的距离结合锌的异羟肟酸基团和帽结构对于抑制HDAC的活性和类别选择性都很重要。具有代表性的化合物（30w）显示出强效的p21启动子活性，与曲古抑菌素A（TSA）相当，
• Fluoride recognition by a chiral urea receptor linked to a phthalimide chromophore
  作者：Raúl Pérez-Ruiz、Yrene Díaz、Bernd Goldfuss、Dirk Hertel、Klaus Meerholz、Axel G. Griesbeck

  DOI：10.1039/b908433a

  日期：——

  procedure involving a Curtius rearrangement. Its photophysical properties were estimated in several solvents. Sensor 1 detected fluoride with absorption as well as fluorescence changes and was only observable for this case and not for other halides. The appearance of a new CT complex emission at a longer wavelength and no changes in the singlet lifetime of 1 in the presence of fluoride supported a fluorescence

  使用涉及库尔修斯重排的有效方法合成了基于具有立体生成中心的尿素活化的邻苯二甲酰亚胺的阴离子化学传感器1。在几种溶剂中估计了其光物理性质。传感器1检测到氟化物具有吸收以及荧光变化，仅在这种情况下可观察到，而对其他卤化物则无法观察到。一个新的CT复杂发射在较长波长和外观中的单线态寿命不可更改1中的氟化物的存在支撑的荧光静态猝灭机制。1 H-NMR研究以及基于DFT方法的B3lYP / 6–31G *理论水平的理论计算，证实了[ 1 -F]的形成−在识别过程中通过H键相互作用而不是受体去质子作用而复杂。加入质子溶剂后观察到该过程的可逆性。
• 1,3-DIOXOISOINDOLE DERIVATIVES HAVING SELECTIVE ANTAGONISM OF T-TYPE CALCIUM CHANNEL
  申请人：Cho Yong Seo

  公开号：US20070259867A1

  公开（公告）日：2007-11-08

  The present invention relates to 1,3-dioxoisoindole derivatives of Formula (1) or pharmaceutically acceptable salts thereof, a preparation method thereof and use thereof as a T-type calcium channel antagonist, based on the fact that 1,3-dioxoisoindole derivatives of Formula (1) show selective antagonistic activity against T-type calcium channel, thus being effective in treating brain diseases, cardiac diseases and neurogenic pains: wherein R 1 is a phenyl or a benzyl group, optionally substituted with a moiety selected from the group consisting of a halogen atom, a C 1 -C 6 alkoxy, a C 1 -C 6 alkyl, and a cyano group; R 2 is a heterocyclic group selected from the group consisting of piperidinyl, pyrrolidinyl, morpholinyl, and piperazinyl groups, wherein the heterocyclic group is optionally substituted with a C 1 -C 6 alkyl group; and n is 1 or 2.

  本发明涉及公式（1）的1,3-二氧杂异吲哚衍生物或其药学上可接受的盐，其制备方法和用作T型钙通道拮抗剂的用途，基于公式（1）的1,3-二氧杂异吲哚衍生物显示出选择性拮抗T型钙通道的活性，因此对治疗脑部疾病，心脏疾病和神经痛有效。其中，R1是苯基或苄基，可选地被取代为来自卤素原子，C1-C6烷氧基，C1-C6烷基和氰基的基团中选出的一个基团；R2是选自哌啶基，吡咯烷基，吗啉基和哌嗪基的杂环基团，其中该杂环基团可选地被C1-C6烷基取代；n为1或2。
• 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。