5-chloro-1-(4-methylbenzyl)indoline-2,3-dione | 79183-51-0

• 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-chloro-1-(4-methylbenzyl)indoline-2,3-dione
• 英文别名: 5-chloro-1-[(4-methylphenyl)methyl]indole-2,3-dione
• CAS: 79183-51-0
• 化学式: C₁₆H₁₂ClNO₂
• mdl: MFCD02315134
• 分子量: 285.73
• InChiKey: JCSBGVTYYVKKJG-UHFFFAOYSA-N

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：

  4-(4-氯苯)-3-氨基硫脲 、 5-chloro-1-(4-methylbenzyl)indoline-2,3-dione 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以86%的产率得到2-(5-chloro-1-(4-methylbenzyl)-2-oxoindolin-3-ylidene)-N-(4-chlorophenyl)hydrazine carbothioamide
  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
• 作为产物：
  描述：

  对氯苯胺 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-chloro-1-(4-methylbenzyl)indoline-2,3-dione
  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

• Chiral CNN Pincer Palladium(II) Complexes with 2-Aryl-6-(oxazolinyl)pyridine Ligands: Synthesis, Characterization, and Application to Enantioselective Allylation of Isatins and Suzuki–Miyaura Coupling Reaction
  作者：Tao Wang、Xin-Qi Hao、Juan-Juan Huang、Kai Wang、Jun-Fang Gong、Mao-Ping Song

  DOI：10.1021/om400945d

  日期：2014.1.13

  1-naphthyl) ligands 2a–f were conveniently prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a–f with PdCl2 in toluene in the presence of sodium bicarbonate afforded the corresponding CNN pincer Pd(II) complexes 3a–f via aryl C–H bond activation of the related ligands. All of the new compounds have been fully characterized by elemental analysis (MS for ligands), 1H

  从市售的6-溴-2-吡啶啉醛中分两步方便地制备了一系列手性2-芳基-6-（恶唑啉基）吡啶（芳基=苯基或1-萘基）配体2a – f。在碳酸氢钠存在下，2a – f与PdCl 2在甲苯中的反应通过相关配体的芳基C–H键活化，提供了相应的CNN钳位Pd（II）配合物3a – f。所有新化合物均已通过元素分析（配体的质谱），1 H和13 C NMR和IR光谱进行了全面表征。此外，Pd（II）配合物3c – f的分子结构已经通过X射线单晶衍射确定。所获得的手性钳催化剂成功地用于靛红与烯丙基三丁基锡的不对称烯丙基化，以高收率得到相应的3-烯丙基-3-羟基羟吲哚，对映选择性高达86％ee。这些钳子还可以催化不对称的Suzuki-Miyaura偶联反应，以高收率和良好的立体选择性（高达ee的68％）提供轴向手性联芳基产品。
• 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
• Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3
  作者：Maria Damgaard、Anas Al-Khawaja、Stine B. Vogensen、Andreas Jurik、Maarten Sijm、Maria E. K. Lie、Mathias I. Bæk、Emil Rosenthal、Anders A. Jensen、Gerhard F. Ecker、Bente Frølund、Petrine Wellendorph、Rasmus P. Clausen

  DOI：10.1021/acschemneuro.5b00150

  日期：2015.9.16

  Screening a library of small-molecule compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [H-3]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC50 values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacological characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a molecular modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes.
• 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.