5-fluoro-1-(4-trifluoromethylbenzyl)isatin | 522612-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-fluoro-1-(4-trifluoromethylbenzyl)isatin
• 英文别名: 5-Fluoro-1-(4-(trifluoromethyl)benzyl)indoline-2,3-dione；5-fluoro-1-[[4-(trifluoromethyl)phenyl]methyl]indole-2,3-dione
• CAS: 522612-14-2
• 化学式: C₁₆H₉F₄NO₂
• 分子量: 323.247
• InChiKey: QLYLKQJDCWBWGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 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：
  6

反应信息

• 作为反应物：
  描述：

  5-fluoro-1-(4-trifluoromethylbenzyl)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-2-oxo-1-(4-trifluoromethyl-benzyl)-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 、 1-溴-三氟对二甲苯 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 0.17h， 生成 5-fluoro-1-(4-trifluoromethylbenzyl)isatin
  参考文献：
  名称：

  Discovery of the First Highly M5-Preferring Muscarinic Acetylcholine Receptor Ligand, an M5 Positive Allosteric Modulator Derived from a Series of 5-Trifluoromethoxy N-Benzyl Isatins

  摘要：

  This report describes the discovery and initial characterization of the first positive allosteric modulator of muscarinic acetylcholine receptor subtype 5 (mAChR5 or M5). Functional HTS, identified VU0119498, which displayed micromolar potencies for potentiation of acetylcholine at M1, M3, and M5 receptors in cell-based Ca2+ mobilization assays. Subsequent optimization led to the discovery of VU0238429, which possessed an EC50 of approximately 1.16 mu M at M5 with >30-fold selectivity versus M1 and M3, with no M2 or M4 potentiator activity.

  DOI：

  10.1021/jm900286j