methyl (5-fluoro-2,4-dinitrophenyl)acetate | 150544-00-6

• 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: methyl (5-fluoro-2,4-dinitrophenyl)acetate
• 英文别名: methyl 2-(5-fluoro-2,4-dinitrophenyl)acetate
• CAS: 150544-00-6
• 化学式: C₉H₇FN₂O₆
• 分子量: 258.163
• InChiKey: GXQXQJUREOKWIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (5-fluoro-2,4-dinitrophenyl)acetate 在 四氢吡咯 、 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 13.25h， 生成 5-((5-fluoro-6-(3-(4-methoxybenzoyl)ureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia

  摘要：

  A series of 6-acylureido derivatives containing a 3-(pyrrol-2-ylmethylidene)indolin-2-one scaffold were synthesized as potential dual Aurora B/FLT3 inhibitors by replacing the 6-arylureido moiety in 6-arylureidoindolin-2-one-based multi-kinase inhibitors. (Z)-N-(2-(pyrrolidin-l-yl)ethyl)-5-((6-(3-(2-fluoro-4-methoxybenzoyflureido)-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (54) was identified as a dual Aurora B/FLT3 inhibitor (IC50 = 0.4 nM and 0.5 nM, respectively). Compound 54 also exhibited potent cytotoxicity with single-digit nanomolar IC50 values against the FLT3 mutant-associated human acute myeloid leukemia (AML) cell lines MV4-11 (FLT3-ITD) and MOLM-13 (FLT3-ITD). Compound 54 also specifically induced extrinsic apoptosis by inhibiting the phosphorylation of the Aurora B and FLT3 pathways in MOLM-13 cells. Compound 54 had a moderate pharmacokinetic profile. The mesylate salt of 54 efficiently inhibited tumor growth and reduced the mortality of BALB/c nude mice (subcutaneous xenograft model) that had been implanted with AML MOLM-13 cells. Compound 54 is more potent than sunitinib not only against FLT3-WT AML cells but also active against sunitinib-resistant FLT3-ITD AML cells. This study demonstrates the significance of dual Aurora B/FLT3 inhibitors for the development of potential agents to treat AML. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.07.108
• 作为产物：
  描述：

  3-氟苯乙酸 在 硫酸 、 硝酸 作用下， 以 甲醇 、 sodium hydroxide 、 乙酸乙酯 为溶剂， 生成 methyl (5-fluoro-2,4-dinitrophenyl)acetate
  参考文献：
  名称：

  Substituted indolinones useful as herbicidal agents

  摘要：

  描述了一种有效控制不良植物物种的替代吲哚酮化合物。还描述了这些化合物的除草用途方法和制备方法。

  公开号：

  US05252536A1

文献信息

• INDOLIN-2-ONE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  申请人：ANNJI PHARMACEUTICAL CO., LTD.

  公开号：US20130281451A1

  公开（公告）日：2013-10-24

  A novel class of indoline-2-one derivatives are disclosed. These compounds are protein kinase inhibitors which are useful for treating hyperproliferative diseases such as cancer.

  揭示了一类新型的吲哚啉-2-酮衍生物。这些化合物是蛋白激酶抑制剂，可用于治疗癌症等过度增殖性疾病。
• Preparation and alkylation of regioisomeric tetrahydrophthalimide-substituted indolin-2(3<i>H</i>)-ones
  作者：Gary M. Karp、Michael E. Condon

  DOI：10.1002/jhet.5570310639

  日期：1994.11

  A series of novel regioisomeric tetrahydrophthalimide-substituted indolin-2-ones has been prepared via the Sommelet-Hauser type cyclization of appropriately substituted anilines as potential herbicides. The resultant indolin-2-ones were then regioselectively alkylated at N-1 and C-3 to give 1,3,3-trisubstituted indolin-2-ones. The most active series was also prepared by the bis-nitration of m-fluorophenylacetic

  已经通过适当取代的苯胺作为潜在除草剂的Sommelet-Hauser型环化反应制备了一系列新颖的区域异构的四氢邻苯二甲酰亚胺取代的吲哚-2-酮。然后将所得的吲哚-2-酮在N-1和C-3区域选择性烷基化，得到1,3,3-三取代的吲哚-2-酮。还制备了最活跃的系列由二的-nitration米-fluorophenylacetic酸接着还原和环化，得到6-氨基-5-氟二氢-2-酮。精制四氢邻苯二甲酰亚胺取代的吲哚-2-酮，然后进行C-和N-烷基化，得到所需化合物。
• Functionally selective alpha2C adrenoreceptor agonists
  申请人：McCormick D. Kevin

  公开号：US20070099872A1

  公开（公告）日：2007-05-03

  In its many embodiments, the present invention provides a novel class of indolines as inhibitors of α2C adrenergic receptor agonists, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more conditions associated with the α2C adrenergic receptors using such compounds or pharmaceutical compositions.

  在其许多实施方式中，本发明提供了一种新型的吲哚烷类化合物，作为α2C肾上腺素能受体激动剂的抑制剂，制备这种化合物的方法，含有一种或多种这种化合物的制药组合物，制备包含一种或多种这种化合物的制药制剂的方法，以及使用这种化合物或制药组合物的方法，用于治疗、预防、抑制或缓解与α2C肾上腺素能受体相关的一种或多种疾病。
• Indolin-2-one derivatives as protein kinase inhibitors
  申请人：Annji Pharmaceutical Co., Ltd.

  公开号：US08946282B2

  公开（公告）日：2015-02-03

  A novel class of indoline-2-one derivatives are disclosed. These compounds are protein kinase inhibitors which are useful for treating hyperproliferative diseases such as cancer. In one aspect, the invention relates to a compound a compound of Formula A: or a pharmaceutically acceptable salt thereof, wherein: Ra is hydrogen, (C6-C18)aryl, halo(C6-C18)aryl, or (C1-C6)alkoxy(C6-C18)aryl; Rb is hydrogen, (C3-C18)heteroaryl, (C1-C6)alkoxy(C3-C18)heteroaryl; (C1-C6)alkyl(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxy(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)carboxyalkyl(C3-C18)heteroaryl; (C1-C6)alkyl(C1-C6)alkylamino(C1-C6)alkylcarbamoyl)(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C18)aryl(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxycarbonyl)(C3-C18)heteroaryl, (C1-C6)alkyl(C1-C6)alkoxy(C1-C6)oxyalkyl(C3-C18)heteroaryl, (C1-C6)alkyl(C3-C6)heterocyclylcarbonyl(C3-C18)heteroaryl, (C1-C6)alkyl(C3-C6)heterocyclyl(C1-C6)oxyalkyl(C3-C18)heteroaryl, or (C1-C6)alkyl((C3-C6)heterocyclyl(C1-C6)alkylcarbamoyl)(C3-C18)heteroaryl; Rc is hydrogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido; Rd is hydrogen, halogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido; Re is-hydrogen, benzoylureido, halobenzoylureido, halo(C1-C6)alkoxybenzoylureido, (C1-C6)alkoxybenzoylureido, (C1-C6)alkylaminobenzoylureido, (C1-C6)alkylbenzoylureido, nitrobenzoylureido, (C1-C6)haloalkylbenzoylureido, (C1-C6)haloalkylhalobenzoylureido, halo(C6-C18)arylcarbomylacetamido, (C1-C6)alkoxy(C6-C18)arylcarbomylacetamido, (C1-C6)alkoxy(C6-C18)arylcarbamoyl(C3-C6)cycloalkylamido, halo(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, (C3-C6)cycloalkyl(C3-C18)heteroarylcarbonylamino, (C1-C6)alkylamino(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, halo(C1-C6)alkoxy(C6-C18)aryl(C3-C18) heteroarylcarbonylamino, (C1-C6)alkoxy(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, (C1-C6)alkyl(C3-C18)heteroarylcarbonylamino, aryl(C3-C18)heteroarylcarbonylamino, (C1-C6)haloalkylhalo(C6-C18)aryl(C3-C6)heterocyclylcarbonylamino, (C1-C6)haloalkyl(C6-C18)aryl(C3-C18)heteroarylcarbonylamino, halo(C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)oxyalkyl(C3-C6)heterocyclylamido, (C1-C6)alkoxy(C1-C6)alkyl(C3-C18)heteroarylamido, (C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)alkyl(C1-C18)aryl(C3-C18)heteroarylamido, (C1-C6)haloalkyl(C6-C18)aryl(C3-C18)heteroarylamido, (C1-C6)alkyl(C3-C18)heteroarylamido, or (C1-C6)alkoxy(C6-C18)aryl(C3-C18)heteroarylamido; and Rf is hydrogen, (C1-C6)alkoxybenzoylureido, or halo(C6-C18)aryl(C3-C18)heteroarylamido.

  本发明揭示了一类新型的吲哚啉-2-酮衍生物。这些化合物是蛋白激酶抑制剂，可用于治疗癌症等增殖性疾病。在一个方面，本发明涉及化合物A的化合物或其药学上可接受的盐，其中：Ra是氢、(C6-C18)芳基、卤代(C6-C18)芳基或(C1-C6)烷氧基(C6-C18)芳基；Rb是氢、(C3-C18)杂环芳基、(C1-C6)烷氧基(C3-C18)杂环芳基、(C1-C6)烷基(C3-C18)杂环芳基、(C1-C6)烷基(C1-C6)烷氧基(C3-C18)杂环芳基、(C1-C6)烷基(C1-C6)羧基烷基(C3-C18)杂环芳基、(C1-C6)烷基(C1-C6)烷基氨基(C1-C6)烷基氨基甲酰基)(C3-C18)杂环芳基、(C1-C6)烷基(C1-C18)芳基(C3-C18)杂环芳基、(C1-C6)烷基(C1-C6)烷氧羰基)(C3-C18)杂环芳基、(C1-C6)烷基(C1-C6)烷氧基(C1-C6)氧基烷基(C3-C18)杂环芳基、(C1-C6)烷基(C3-C6)杂环烷基羰基(C3-C18)杂环芳基、(C1-C6)烷基(C3-C6)杂环芳基(C1-C6)氧基烷基(C3-C18)杂环芳基或(C1-C6)烷基((C3-C6)杂环芳基(C1-C6)烷基氨基甲酰基)(C3-C18)杂环芳基；Rc是氢、(C1-C6)烷氧基苯甲酰脲基或卤代(C6-C18)芳基(C3-C18)杂环芳基酰胺基；Rd是氢、卤素、(C1-C6)烷氧基苯甲酰脲基或卤代(C6-C18)芳基(C3-C18)杂环芳基酰胺基；Re是氢、苯甲酰脲基、卤代苯甲酰脲基、卤代(C1-C6)烷氧基苯甲酰脲基、(C1-C6)烷氧基苯甲酰脲基、(C1-C6)烷基氨基苯甲酰脲基、(C1-C6)烷基苯甲酰脲基、硝基苯甲酰脲基、(C1-C6)卤代烷基苯甲酰脲基、(C1-C6)卤代烷基卤代苯甲酰脲基、卤代(C6-C18)芳基羧酰乙酰胺基、(C1-C6)烷氧(C6-C18)芳基羧酰乙酰胺基、(C1-C6)烷氧(C6-C18)芳基氨基甲酰基(C3-C6)环烷基酰胺基、卤代(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C3-C6)环烷基(C3-C18)杂环芳基酰胺基、(C1-C6)烷基氨基(C6-C18)芳基(C3-C18)杂环芳基酰胺基、卤代(C1-C6)烷氧(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)烷氧(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)烷基(C3-C18)杂环芳基酰胺基、芳基(C3-C18)杂环芳基酰胺基、(C1-C6)卤代烷基卤代(C6-C18)芳基(C3-C6)杂环烷基酰胺基、(C1-C6)卤代烷基(C6-C18)芳基(C3-C18)杂环芳基酰胺基、卤代(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)氧基烷基(C3-C6)杂环酰胺基、(C1-C6)烷氧(C1-C6)烷基(C3-C18)杂环芳基酰胺基、(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)烷基(C1-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)卤代烷基(C6-C18)芳基(C3-C18)杂环芳基酰胺基、(C1-C6)烷基(C3-C18)杂环芳基酰胺基或(C1-C6)烷氧(C6-C18)芳基(C3-C18)杂环芳基酰胺基；Rf是氢、(C1-C6)烷氧基苯甲酰脲基或卤代(C6-C18)芳基(C3-C18)杂环芳基酰胺基。
• WO2007/24944
  申请人：——

  公开号：——

  公开（公告）日：——