5-fluoro-1-(4-fluorobenzyl)isatin | 522612-13-1

• 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: 5-fluoro-1-(4-fluorobenzyl)isatin
• 英文别名: 5-Fluoro-1-[(4-fluorophenyl)methyl]indole-2,3-dione
• CAS: 522612-13-1
• 化学式: C₁₅H₉F₂NO₂
• 分子量: 273.239
• InChiKey: BXGOCGPRTMXSHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-fluoro-1-(4-fluorobenzyl)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 Cyano-[5-fluoro-1-(4-fluoro-benzyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-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：

  5-氟靛红 、 4-氟氯苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-fluoro-1-(4-fluorobenzyl)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

• Synthesis, spectroscopic investigations, DFT studies, molecular docking and antimicrobial potential of certain new indole-isatin molecular hybrids: Experimental and theoretical approaches
  作者：Maha S. Almutairi、Azza S. Zakaria、P. Primsa Ignasius、Reem I. Al-Wabli、Isaac Hubert Joe、Mohamed I. Attia

  DOI：10.1016/j.molstruc.2017.10.025

  日期：2018.2

  using FT-IR and FT-Raman with the aid of density functional theory approach. The natural bond orbital analysis as well as HOMO and LUMO molecular orbitals investigations of compound 5h were carried out to explore its possible intermolecular delocalization or hyperconjugation and its possible interactions with the target protein. Molecular docking of compound 5h predicted its binding mode with the fungal

  摘要 吲哚-靛红分子杂化物 5a-i 已被合成并通过不同的光谱方法表征，以作为针对一组革兰氏阳性菌、革兰氏阴性菌和霉菌的新型抗菌剂进行评估。选择化合物 5h 作为制备的化合物 5a-i 的代表性实例进行计算研究。借助密度泛函理论方法，使用 FT-IR 和 FT-Raman 研究了其振动特性。进行了化合物5h的自然键轨道分析以及HOMO和LUMO分子轨道研究，以探索其可能的分子间离域或超共轭及其与靶蛋白可能的相互作用。化合物 5h 的分子对接预测了其与真菌靶蛋白的结合模式。
• <p>Antiproliferative activity and possible mechanism of action of certain 5-methoxyindole tethered C-5 functionalized isatins</p>
  作者：Maha S. Almutairi、Eman S. Hassan、Adam B. Keeton、Gary A. Piazza、Ali S. Abdelhameed、Mohamed I. Attia

  DOI：10.2147/dddt.s208241

  日期：——

  Background: Cancer is one of the most dreaded human diseases, that has become an ever-increasing health problem and is a prime cause of death globally. The potential antiproliferative activity of certain indole-isatin molecular hybrids 5a-w was evaluated in vitro against three human cancer cell lines.Methods: Standard protocols were adopted to examine the antiproliferative potential and mechanisms of compounds 5a-w. Western blot analysis was carried out on compound 5o.Results: Compounds 5a-w demonstrated in vitro antiproliferative activity in the range of 22.6-97.8%, with compounds 5o and 5w being the most active antiproliferative compounds with IC50 values of 1.69 and 1.91 mu M, which is fivefold and fourfold more potent than sunitinib (IC50 =8.11 mu M), respectively. Compound 5o was selected for in-depth pharmacological testing to understand its possible mechanism of antiproliferative activity. It caused a lengthening of the G1 phase and a reduction in the S and G2/M phases of the cell cycle and had an IC50 value of 10.4 pM with the resistant NCI-H69AR cancer cell line. Moreover, compound 5o significantly decreased the amount of phosphorylated Rb protein in a dose-dependent fashion, which was confirmed via Western blot analysis.Conclusion: The current investigation highlighted the potential antiproliferative activity of compounds 5a-w as well as the antiproliferative profile of compound 5o. These compounds can be harnessed as new lead antiproliferatives in the preclinical studies of cancer chemotherapy.
• 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.
• Novel, Highly Potent Aldose Reductase Inhibitors:  Cyano(2-oxo-2,3-dihydroindol-3-yl)acetic Acid Derivatives
  作者：Federico Da Settimo、Giampaolo Primofiore、Antonio Da Settimo、Concettina La Motta、Francesca Simorini、Ettore Novellino、Giovanni Greco、Antonio Lavecchia、Enrico Boldrini

  DOI：10.1021/jm030762f

  日期：2003.4.1

  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.