5-bromo-1-(4-methylbenzyl)isatin | 314025-86-0

• 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: 5-bromo-1-(4-methylbenzyl)isatin
• 英文别名: isatin；5-bromo-1-(4-methylbenzyl)-1H-indole-2,3-dione；5-bromo-1-[(4-methylphenyl)methyl]indole-2,3-dione
• CAS: 314025-86-0
• 化学式: C₁₆H₁₂BrNO₂
• mdl: MFCD01248187
• 分子量: 330.181
• InChiKey: DOMIMEKJJZUOOO-UHFFFAOYSA-N

物化性质

• 沸点：
  482.4±55.0 °C(Predicted)
• 密度：
  1.547±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-(4-methylbenzyl)isatin 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 生成 [5-Bromo-1-(4-methyl-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-cyano-acetic acid
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  Cyano(2-oxo-2,3-dihydroindol-3-yl)acetic Acid Derivatives

  摘要：

  Cyano(2-oxo-2,3-dihydroindol-3-yl)acetic acid derivatives were synthesized and tested as a novel class of aldose reductase (ALR2) inhibitors. Each compound was evaluated as a diastereomeric mixture, due to tautomeric equilibria in solution. The parent compound 39 exhibited a good inhibitory activity with an IC50 value of 0.85 muM, similar to that of the well-known ARI sorbinil (IC50 0.50 muM). The concurrent introduction of a halogen and a lipophilic group in the 5- and in the 1-positions, respectively, of the indole nucleus of 39, gave compound 55, cyano[5-fluoro-1-(4-methylbenzyl)-2-oxo-2,3-dihydroindol-3-yl] acetic acid, which displayed the highest activity (IC50 0.075 muM, very close to that of tolrestat IC50 0.046 muM), with a good selectivity toward ALR2 compared with aldehyde reductase (ALR1) (16.4-fold), and no appreciable inhibitory properties against sorbitol dehydrogenase (SD), or glutathione reductase (GR). The isopropyl ester 59, a prodrug of 55, was found to be almost as effective as tolrestat in preventing cataract development in severely galactosemic rats when administered as an eye drop solution. Docking simulation of 55 into a three-dimensional model of human ALR2 made it possible to formulate the hypothesis that the 2-hydroxy tautomer was the active species binding into the catalytic site of the enzyme. This was fully consistent with the structure-activity relationships within this series of cyanooxoindolylacetic acid derivatives.

  DOI：

  10.1021/jm030762f
• 作为产物：
  描述：

  4-溴苯胺 在 硫酸 、 potassium carbonate 、 sodium sulfate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-bromo-1-(4-methylbenzyl)isatin
  参考文献：
  名称：

  Synthesis and cytostatic evaluation of some 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide

  摘要：

  Various substituted 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 4a-g and 2-(5-substituted-1-(4-substituted benzyl)-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 5a-k were synthesized. The compounds were evaluated for their cytostatic activity against human Molt4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Several of these compounds were endowed with low micromolar 50%-inhibitory concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells were also most inhibitory against human T-lymphocyte tumor cells. 2-(5-fluoro-1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-N-p-tolylhydrazine carbothioamide (5b) emerged as the most potent cytostatic compound among the tested compounds. The encouraging cytostatic data provide an adequate rationale for further modification of these molecular scaffolds.

  DOI：

  10.1007/s00044-010-9458-3

文献信息

• Enhancement of the tail hydrophobic interactions within the carbonic anhydrase IX active site via structural extension: Design and synthesis of novel N-substituted isatins-SLC-0111 hybrids as carbonic anhydrase inhibitors and antitumor agents
  作者：Wagdy M. Eldehna、Mahmoud F. Abo-Ashour、Alessio Nocentini、Radwan S. El-Haggar、Silvia Bua、Alessandro Bonardi、Sara T. Al-Rashood、Ghada S. Hassan、Paola Gratteri、Hatem A. Abdel-Aziz、Claudiu T. Supuran

  DOI：10.1016/j.ejmech.2018.10.068

  日期：2019.1

  report the design and synthesis of novel N-substituted isatins-SLC-0111 hybrids (6a-f and 9a-l). A structural extension approach was adopted via N-alkylation and N-benzylation of isatin moiety to enhance the tail hydrophobic interactions within the carbonic anhydrase (CA) IX active site. Thereafter, a hybrid pharmacophore approach was utilized via merging the pharmacophoric elements of isatin and SLC-0111

  本文中，我们报道了新型N-取代的isatins-SLC-0111杂种（6a-f和9a-1）的设计和合成。通过结构化部分的N-烷基化和N-苄基化采用结构延伸方法，以增强碳酸酐酶（CA）IX活性位点内的尾部疏水相互作用。此后，通过将Isatin和SLC-0111的药效学元素合并到一个化学框架中，使用了混合药效学方法。按计划，与N-未取代的铅IVa-c相比，目标杂种（K I s：4.7-86.1 nM）对hCA IX的抑制谱有显着改善（K I s：192–239 nM），达到了。按照计划，设计的杂种分子在CA IX活性位点的分子对接揭示了N-烷基化和N-苄基化的靛红部分适应由T73，P75，P76，L91，L123和A128形成的宽疏水口袋的能力，从而确立了强烈的范德华相互作用。杂种6c在低氧条件下对乳腺癌MDA-MB-231和MCF-7细胞系表现出良好的抗增殖活性（IC 50分别 为7.43±0
• Chiral Phosphoric Acid-Catalyzed Pictet–Spengler Reactions for Synthesis of 5′,11′-Dihydrospiro[indoline-3,6′-indolo[3,2-<i>c</i>]qui-nolin]-2-ones Containing Quaternary Stereocenters
  作者：Xin-Wei Wang、Xiang Li、Mu-Wang Chen、Bo Wu、Yong-Gui Zhou

  DOI：10.1021/acs.joc.1c00289

  日期：2021.5.7

  Chiral phosphoric acid-catalyzed Pictet–Spengler reactions of 2-(1H-indolyl)aniline derivatives and isatins by the condensation/cyclization process have been realized. A series of enantioenriched 5′,11′-dihydrospiro[indoline-3,6′-indolo[3,2-c]quinolin]-2-ones bearing quaternary stereogenic centers were obtained with excellent yields and up to >99% ee. This protocol was suitable for the Pictet–Spengler

  通过缩合/环化过程，实现了手性磷酸催化2-（1 H-吲哚基）苯胺衍生物和靛红的Pictet-Spengler反应。获得了一系列带有季生立体中心的对映体富集的5'，11'-二氢螺[indoline-3,6'-吲哚[3,2- c ]喹啉] -2-酮，具有优异的收率和高达> 99％的ee。该方案适用于2-（1-苄基-5-甲基-1 H-吡咯-2-基）苯胺和各种1'，5'-dihydro-spiro [indoline-3]的Pictet-Spengler反应也可以以良好的产率和高达88％的ee获得，4′-吡咯并[3，2- c ]喹啉] -2-酮。
• 一种包含有吲哚骨架的螺环的手性吲哚啉酮的合成方法
  申请人：中国科学院大连化学物理研究所

  公开号：CN115010565A

  公开（公告）日：2022-09-06

  本发明提供一种包含有吲哚骨架的螺环的手性吲哚啉酮的合成方法，其用到的催化剂是手性磷酸。通过该方法可以得到含有吲哚骨架的螺环的吲哚啉酮(对映体过量可达>99％)。本发明操作简单易行，催化剂商业可得，对映选择性和产率好，具有潜在的应用价值。
• Uncatalyzed One-Pot Synthesis of Highly Substituted Pyridazines and Pyrazoline-Spirooxindoles via Domino SN/Condensation/Aza-ene Addition Cyclization Reaction Sequence
  作者：Nasrin Zohreh、Abdolali Alizadeh

  DOI：10.1021/co400005y

  日期：2013.6.10

  A previously unknown class of highly substituted pyridazines and pyrazoline-spirooxinoles are easily prepared by an uncatalyzed one-pot three-component approach incorporating a domino SN/condensation/aza-ene addition cyclization reaction sequence. 1,1-Dihydrazino-2-nitroethylene (DHNE) which is generated in situ from the nudeophilic substitution (SN) reaction of hydrazine and 1,1-bis(methylthio)-2-nitroethylene (BMTNE), allowed to be condensed with active 1,2-dicarbonyl compounds followed by an intramolecular aza-ene addition cyclization to obtain the titled products depending on the type of 1,2-dicarbonyl. All reactions are easily performed and proceed with high efficiency under very simple and mild conditions without any catalyst and give good yields avoiding time-consuming, costly syntheses, and tedious workup and purification of products.
• Synthesis and cytostatic evaluation of some 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide
  作者：Subhas S. Karki、Amol Kulkarni、Nishith Teraiya、Erik De Clercq、Jan Balzarini

  DOI：10.1007/s00044-010-9458-3

  日期：2011.11

  Various substituted 2-(5-substituted-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 4a-g and 2-(5-substituted-1-(4-substituted benzyl)-2-oxoindolin-3-ylidene)-N-substituted hydrazine carbothioamide 5a-k were synthesized. The compounds were evaluated for their cytostatic activity against human Molt4/C8 and CEM T-lymphocytes as well as murine L1210 leukemia cells. Several of these compounds were endowed with low micromolar 50%-inhibitory concentration (IC50) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells were also most inhibitory against human T-lymphocyte tumor cells. 2-(5-fluoro-1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-N-p-tolylhydrazine carbothioamide (5b) emerged as the most potent cytostatic compound among the tested compounds. The encouraging cytostatic data provide an adequate rationale for further modification of these molecular scaffolds.