5-methyl-4-phenylindoline-2,3-dione | 1164112-34-8

• 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-methyl-4-phenylindoline-2,3-dione
• 英文别名: 5-methyl-4-phenyl-1H-indole-2,3-dione
• CAS: 1164112-34-8
• 化学式: C₁₅H₁₁NO₂
• 分子量: 237.258
• InChiKey: MYJSHNXSQQRVBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-methyl-4-phenylindoline-2,3-dione 、 3,4,5-三甲氧基苯甲酰肼 在 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 3,4,5-trimethoxy-N'-(5-methyl-2-oxo-4-phenylindol-3-yl)benzohydrazide
  参考文献：
  名称：

  Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay

  摘要：

  We report the discovery of a series of substituted N'-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N'-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC50 value of 0.24 mu M in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N'-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.056 mu M in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC50 values of 0.17, 0.088 and 0.14 mu M in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.03.121
• 作为产物：
  描述：

  4-iodo-5-methylindoline-2,3-dione 、 苯硼酸 在 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 0.08h， 以95%的产率得到5-methyl-4-phenylindoline-2,3-dione
  参考文献：
  名称：

  Efficient synthesis of bulky 4-substituted-isatins via microwave-promoted Suzuki cross-coupling reaction

  摘要：

  Indoline-2,3-diones (isatins) and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. Very few examples related to the synthesis of 4-substituted-arylisatins have been reported before. Utilizing microwave irradiation, the synthesis of bulky 4-substituted-arylisatins via a Suzuki cross-coupling has been developed with a wide range of substrates. All the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicating that electronic effects and steric modifications have little effect on this reaction. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2012.12.021

文献信息

• TUMOR NECROSIS FACTOR ALPHA INHIBITORS AND THEIR USE IN THE TREATMENT OF HUMAN DISEASES
  申请人：AVANIR PHARMACEUTICALS

  公开号：EP1996553A2

  公开（公告）日：2008-12-03
• [EN] TUMOR NECROSIS FACTOR ALPHA INHIBITORS AND THEIR USE IN THE TREATMENT OF HUMAN DISEASES<br/>[FR] INHIBITEURS DU FACTEUR DE NÉCROSE TUMORALE ALPHA ET LEURS UTILISATIONS POUR LE TRAITEMENT DE MALADIES HUMAINES
  申请人：AVANIR PHARMACEUTICALS

  公开号：WO2007109251A2

  公开（公告）日：2007-09-27

  [EN] Inhibitors of tumor necrosis factor alpha are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with tumor necrosis factor alpha. The inhibitors of tumor necrosis factor alpha have the following structures: (I) including stereoisomers, pharmaceutically acceptable salts, and solvates thereof, wherein substituents are as defined herein. Compositions containing an inhibitor of tumor necrosis factor alpha in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.
  [FR] L'invention porte sur des inhibiteurs du facteur de nécrose tumorale alpha utiles pour le traitement de divers troubles dont le traitement d'états pathologiques associés audit facteur. Lesdits inhibiteurs présentent les structures (I) dont les substituants sont définis dans la description. L'invention porte également sur leurs stéréoisomères, leurs sels pharmacocompatibles, leurs solvates, sur des compositions les contenant avec un support pharmacocompatibles, et sur leurs méthodes d'utilisation.
• Efficient synthesis of bulky 4-substituted-isatins via microwave-promoted Suzuki cross-coupling reaction
  作者：Yu-Chao Liu、Chen-Jin Ye、Qiong Chen、Guang-Fu Yang

  DOI：10.1016/j.tetlet.2012.12.021

  日期：2013.2

  Indoline-2,3-diones (isatins) and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. Very few examples related to the synthesis of 4-substituted-arylisatins have been reported before. Utilizing microwave irradiation, the synthesis of bulky 4-substituted-arylisatins via a Suzuki cross-coupling has been developed with a wide range of substrates. All the reactions proceeded smoothly and afforded moderate to excellent yields of products, which indicating that electronic effects and steric modifications have little effect on this reaction. (C) 2012 Elsevier Ltd. All rights reserved.
• Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay
  作者：Nilantha Sirisoma、Azra Pervin、John Drewe、Ben Tseng、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2009.03.121

  日期：2009.5

  We report the discovery of a series of substituted N'-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N'-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC50 value of 0.24 mu M in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N'-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.056 mu M in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC50 values of 0.17, 0.088 and 0.14 mu M in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization. (C) 2009 Elsevier Ltd. All rights reserved.