3-(methylthio)-4-nitroindolin-2-one | 40800-70-2

• 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: 3-(methylthio)-4-nitroindolin-2-one
• 英文别名: 3-methylsulfanyl-4-nitro-1,3-dihydro-indol-2-one；4-nitro-3-methylthio-oxindole；3-methylsulfanyl-4-nitro-1,3-dihydroindol-2-one
• CAS: 40800-70-2
• 化学式: C₉H₈N₂O₃S
• 分子量: 224.24
• InChiKey: DQGAFWFNGUKXQJ-UHFFFAOYSA-N

物化性质

• 沸点：
  397.3±42.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(methylthio)-4-nitroindolin-2-one 在 tin(II) chloride dihdyrate 、 溶剂黄146 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 9.0h， 生成 4-methoxy-N-(2-oxoindolin-4-ylcarbamoyl)benzamide
  参考文献：
  名称：

  INDOLIN-2-ONE DERIVATIVES AS PROTEIN KINASE INHIBITORS

  摘要：

  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。

  公开号：

  US20130281451A1
• 作为产物：
  描述：

  2-(2-amino-6-nitrophenyl)-2-(methylthio)acetamide 在 盐酸 作用下， 以 水 为溶剂， 生成 3-(methylthio)-4-nitroindolin-2-one
  参考文献：
  名称：

  N-氯邻苯二甲酰亚胺作为Gassman芳族烷基邻烷基化反应中温和有效的氯化试剂。3-（甲硫基）氧吲哚的合成

  摘要：

  据报道，对Gassman 3-（甲硫基）恶唑合成有实际的改进。在我们的方法中，将取代的苯胺与2-（甲硫基）乙酰胺在温和的反应条件下，在作为氯化剂的N-氯邻苯二甲酰亚胺存在下反应，生成α-酰胺基硫化物，然后将其环化为得到3-（甲硫基）氧吲哚。该方法已成功地用于关键中间体2-（2-氨基-3-苯甲酰基苯基）-2-（甲硫基）乙酰胺的合成，在制备常用的眼科药物奈帕芬酸的过程中。

  DOI：

  10.1016/j.tetlet.2014.08.044

文献信息

• Isatin products
  申请人：The Regents of the University of Minnesota

  公开号：US04186132A1

  公开（公告）日：1980-01-29

  An aniline is converted to a 3-lower hydrocarbonthiooxindole by processes already known in the art, the product converted to a 3-halo-3-lower hydrocarbonthiooxindole by oxidative halogenation, and the product subjected to hydrolysis to form the desired isatins.

  一种苯胺通过已知的方法转化为3-较低碳氢基硫代吲哚，该产物通过氧化卤代反应转化为3-卤代-3-较低碳氢基硫代吲哚，然后将产物进行水解反应形成所需的吲哚酮。
• Isatin process and products
  申请人：Regents of University of Minnesota

  公开号：US04188325A1

  公开（公告）日：1980-02-12

  An aniline is converted to a 3-lower hydrocarbonthiooxindole by processes already known in the art, the product converted to a 3-halo-3-lower hydrocarbonthiooxindole by oxidative halogenation, and the product subjected to hydrolysis to form the desired isatins.

  一种苯胺通过已知的工艺转化为3-较低碳氢基硫代吲哚，该产物通过氧化卤代反应转化为3-卤代-3-较低碳氢基硫代吲哚，然后将产物经过水解作用形成所需的吲哚。
• 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。
• Novel acylureidoindolin-2-one derivatives as dual Aurora B/FLT3 inhibitors for the treatment of acute myeloid leukemia
  作者：Ajit Dhananjay Jagtap、Pei-Teh Chang、Jia-Rong Liu、Hsiao-Chun Wang、Nagendra B. Kondekar、Li-Jiuan Shen、Hsiang-Wen Tseng、Grace Shiahuy Chen、Ji-Wang Chern

  DOI：10.1016/j.ejmech.2014.07.108

  日期：2014.10

  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.
• New generation dopaminergic agents. 5. heterocyclic bioisosteres that exploit the 3-OH-N1-phenylpiperazine dopaminergic template
  作者：Richard E. Mewshaw、Antoine Verwijs、Xiaojie Shi、Georgia B. McGaughey、James A. Nelson、Hossein Mazandarani、Julie A. Brennan、Karen L. Marquis、Joseph Coupet、Terrance H. Andree

  DOI：10.1016/s0960-894x(98)00474-0

  日期：1998.10

  The synthesis of several bioisosteric analogs based on the 3-OH-N'-phenylpiperazine dopamine D-2 agonist template (i.e., 4) is described. The indolone (5) and 2-CF3-benzimidazole (13) were observed to have: excellent affinity for the D-2 receptor. Several Dq selective compounds were also identified. Molecular modeling studies and a putative bioactive conformation are discussed. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.

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