(3Z)-5-methoxy-1H-indole-2,3-dione 3-[(4-isopropylphenyl)hydrazone] | 1263428-97-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3Z)-5-methoxy-1H-indole-2,3-dione 3-[(4-isopropylphenyl)hydrazone]
• 英文别名: 5-methoxy-3-[2-(4-propan-2-ylphenyl)hydrazinyl]indol-2-one
• CAS: 1263428-97-2
• 化学式: C₁₈H₁₉N₃O₂
• 分子量: 309.368
• InChiKey: PZDJROXHSXZRPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.72
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3Z)-5-methoxy-1H-indole-2,3-dione 3-[(4-isopropylphenyl)hydrazone] 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以97%的产率得到(3Z)-5-hydroxy-1H-indole-2,3-dione 3-[(4-isopropylphenyl)hydrazone]
  参考文献：
  名称：

  Synthesis and biophysical evaluation of arylhydrazono-1H-2-indolinones as β-amyloid aggregation inhibitors

  摘要：

  A series of isatin-3-arylhydrazones were synthesized and evaluated in vitro as inhibitors of A beta(1-40) aggregation using a thioflavin T fluorescence method. An exploration of the effects on A beta(1-40) aggregation of a number of diverse substituents at phenylhydrazone group and 5,6- positions of the indolinone nucleus led us to single out some new anti-aggregating compounds with IC50 values in the low micromolar range. The most active compounds carry methoxy- or hydroxy- substituents in the indolinone 5,6-positions and lipophilic groups such as iPr and Cl at 4'- and 3'-position, respectively, of the phenylhydrazone moiety. Two derivatives are noteworthy, namely 18 (IC50 = 0.4 mu M) and 42 (IC50 = 1.1 mu M). The in vitro effects of the highly active, water soluble, compound 42 on the temporal evolution of A beta(1-40) fibrils formation were further investigated by circular dichroism spectroscopy, transmission electron microscopy and dynamic light scattering studies, which clearly showed that this compound delayed and lowered the amyloid fibril formation. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.015
• 作为产物：
  描述：

  5-甲氧基靛红 、 4-异丙基苯肼盐酸盐 以 甲醇 为溶剂， 以70%的产率得到(3Z)-5-methoxy-1H-indole-2,3-dione 3-[(4-isopropylphenyl)hydrazone]
  参考文献：
  名称：

  Synthesis and biophysical evaluation of arylhydrazono-1H-2-indolinones as β-amyloid aggregation inhibitors

  摘要：

  A series of isatin-3-arylhydrazones were synthesized and evaluated in vitro as inhibitors of A beta(1-40) aggregation using a thioflavin T fluorescence method. An exploration of the effects on A beta(1-40) aggregation of a number of diverse substituents at phenylhydrazone group and 5,6- positions of the indolinone nucleus led us to single out some new anti-aggregating compounds with IC50 values in the low micromolar range. The most active compounds carry methoxy- or hydroxy- substituents in the indolinone 5,6-positions and lipophilic groups such as iPr and Cl at 4'- and 3'-position, respectively, of the phenylhydrazone moiety. Two derivatives are noteworthy, namely 18 (IC50 = 0.4 mu M) and 42 (IC50 = 1.1 mu M). The in vitro effects of the highly active, water soluble, compound 42 on the temporal evolution of A beta(1-40) fibrils formation were further investigated by circular dichroism spectroscopy, transmission electron microscopy and dynamic light scattering studies, which clearly showed that this compound delayed and lowered the amyloid fibril formation. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.11.015

文献信息

• Insights into Structure-Activity Relationships of 3-Arylhydrazonoindolin-2-One Derivatives for Their Multitarget Activity on β-Amyloid Aggregation and Neurotoxicity
  作者：Rosa Purgatorio、Modesto de Candia、Annalisa De Palma、Francesco De Santis、Leonardo Pisani、Francesco Campagna、Saverio Cellamare、Cosimo Altomare、Marco Catto

  DOI：10.3390/molecules23071544

  日期：——

  3-(2-arylhydrazono)indolin-2-one derivatives was synthesized and assayed, investigating the effects of substitutions on both the indole core and arylhydrazone moiety. Compared with the reference compound 1, we disclosed equipotent derivatives bearing alkyl substituents at the indole nitrogen, and fairly tolerated bioisosteric replacements at the arylhydrazone moiety. For most of the investigated compounds

  尽管迄今为止进行的临床试验存在争议，但通过寻找小分子Aβ聚集抑制剂来预防β淀粉样蛋白（Aβ）沉积和神经毒性仍然是寻找有效治疗阿尔茨海默氏病（AD）及其相关药物的目标。神经变性综合征。作为先前研究的延续，合成并测定了一系列新的3-（2-芳基hydr基）吲哚-2-酮衍生物，研究了取代基对吲哚核心和芳基moiety部分的影响。与参考化合物1相比，我们公开了在吲哚氮上带有烷基取代基和在芳基moiety部分上具有相当耐受性的生物等位取代基的等价衍生物。对于大多数研究的化合物，通过双线性关系，通过反相HPLC方法评估，发现Aβ40聚集的抑制作用（表示为pIC50）与亲脂性相关。N 1-环丙基衍生物28在Aβ42低聚物毒性和过氧化氢诱导的氧化应激的基于细胞的试验中进行了测试，显示出显着的细胞保护作用。这项研究证实了isatin在制备可影响AD涉及的不同生化途径的多靶标小分子中的多功能性。
• Synthesis and biophysical evaluation of arylhydrazono-1H-2-indolinones as β-amyloid aggregation inhibitors
  作者：Francesco Campagna、Marco Catto、Rosa Purgatorio、Cosimo D. Altomare、Angelo Carotti、Angelo De Stradis、Gerardo Palazzo

  DOI：10.1016/j.ejmech.2010.11.015

  日期：2011.1

  A series of isatin-3-arylhydrazones were synthesized and evaluated in vitro as inhibitors of A beta(1-40) aggregation using a thioflavin T fluorescence method. An exploration of the effects on A beta(1-40) aggregation of a number of diverse substituents at phenylhydrazone group and 5,6- positions of the indolinone nucleus led us to single out some new anti-aggregating compounds with IC50 values in the low micromolar range. The most active compounds carry methoxy- or hydroxy- substituents in the indolinone 5,6-positions and lipophilic groups such as iPr and Cl at 4'- and 3'-position, respectively, of the phenylhydrazone moiety. Two derivatives are noteworthy, namely 18 (IC50 = 0.4 mu M) and 42 (IC50 = 1.1 mu M). The in vitro effects of the highly active, water soluble, compound 42 on the temporal evolution of A beta(1-40) fibrils formation were further investigated by circular dichroism spectroscopy, transmission electron microscopy and dynamic light scattering studies, which clearly showed that this compound delayed and lowered the amyloid fibril formation. (C) 2010 Elsevier Masson SAS. All rights reserved.