4-甲基吲哚酮 | 13220-46-7

• 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
• 中文名称: 4-甲基吲哚酮
• 中文别名: 4-甲基氧化吲哚；4-甲基吲哚啉-2-酮
• 英文名称: 4-methyl-1,3-dihydro-indol-2-one
• 英文别名: 4-methylindolin-2-one；4-methyl-2-oxo-1,2-dihydro-indole；4-methyl-1,3-dihydroindol-2-one
• CAS: 13220-46-7
• 化学式: C₉H₉NO
• mdl: MFCD09835631
• 分子量: 147.177
• InChiKey: USRZZPHRQZGXFH-UHFFFAOYSA-N

物化性质

• 熔点：
  211 °C
• 沸点：
  318.4±41.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  4-甲基吲哚酮 在 tris-(dibenzylideneacetone)dipalladium(0) 、 硼烷四氢呋喃络合物 、 potassium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 N,N-二甲基乙酰胺 为溶剂， 反应 54.0h， 生成
  参考文献：
  名称：

  Discovery of Novel Indoline Cholesterol Ester Transfer Protein Inhibitors (CETP) through a Structure-Guided Approach

  摘要：

  Using the collective body of known (CETP) inhibitors as inspiration for design, a structurally novel series of tetrahydroquinoxaline CETP inhibitors were discovered. An exemplar from this series, compound 5, displayed potent in vitro CETP inhibition and was efficacious in a transgenic cynomologus-CETP mouse HDL PD (pharinacodynamic) assay. However, an undesirable metabolic profile and chemical instability hampered further development of the series. A three-dimensional structure of tetrahydroquinoxaline inhibitor 6 was proposed from H-1 NMR structural studies, and this model was then used in silico for the design of a new class of compounds based upon an indoline scaffold. This work resulted in the discovery of compound 7, which displayed potent in vitro CETP inhibition, a favorable PK-PD profile relative to tetrahydroquinoxaline 5, and dose-dependent efficacy in the transgenic cynomologus-CETP mouse HDL PD assay.

  DOI：

  10.1021/acsmedchemlett.5b00404
• 作为产物：
  描述：

  邻甲基苯乙酰氯 在 palladium on activated charcoal 次氯酸叔丁酯 、 氢气 、 sodium carbonate 、 silver carbonate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 5.83h， 生成 4-甲基吲哚酮
  参考文献：
  名称：

  Electrophilic aromatic substitution with N-methoxy-N-acylnitrenium ions generated from N-chloro-N-methoxy amides: syntheses of nitrogen heterocyclic compounds bearing a N-methoxy amide group

  摘要：

  DOI：

  10.1021/jo00275a027

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：UCL BUSINESS LTD

  公开号：WO2019243841A1

  公开（公告）日：2019-12-26

  The present invention relates to compounds, compositions, combinations and medicaments containing said compounds and processes for their preparation. The invention also relates to the use of said compounds, combinations, compositions and medicaments, for example as modulators of alpha 1 antitrypsin and treating diseases associated with alpha antitrypsin, particularly liver diseases.

  本发明涉及含有所述化合物的化合物、组合物、组合物和药物以及其制备方法。该发明还涉及所述化合物、组合物、组合物和药物的用途，例如作为α1抗胰蛋白酶的调节剂和用于治疗与α抗胰蛋白酶相关的疾病，特别是肝脏疾病。
• [EN] METHODS AND COMPOSITIONS FOR INHIBITION OF RAS<br/>[FR] MÉTHODES ET COMPOSITIONS PERMETTANT L'INHIBITION DE LA RAS
  申请人：ARAXES PHARMA LLC

  公开号：WO2016049568A1

  公开（公告）日：2016-03-31

  Inhibitors of Ras protein, methods to modulate the activity of Ras protein, and methods of treatment of disorders mediated by Ras protein are provided. A method for regulating activity of a K-Ras, H-Ras or N-Ras mutant protein with a compound is described. Disorders that can be treated include cancer, such as hematological cancer, pancreatic cancer, MYH associated polyposis, colorectal cancer, or lung cancer.

  提供了Ras蛋白的抑制剂，调节Ras蛋白活性的方法，以及通过Ras蛋白介导的疾病治疗方法。描述了一种使用化合物调节K-Ras、H-Ras或N-Ras突变蛋白活性的方法。可治疗的疾病包括癌症，如血液癌症、胰腺癌、MYH相关性息肉症、结直肠癌或肺癌。
• 3-heteroarylidene-2-indolinone protein kinase inhibitors
  申请人：Sugen, Inc.

  公开号：US06486185B1

  公开（公告）日：2002-11-26

  The present invention relates to novel 3-heteroarylidene-2-indolinone compounds and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新颖的3-杂环亚烯基-2-吲哚酮化合物及其生理上可接受的盐，这些化合物调节蛋白激酶的活性，因此预计在预防和治疗蛋白激酶相关的细胞疾病，如癌症方面具有用处。
• Formulations for pharmaceutical agents ionizable as free acids or free bases
  申请人：Shenoy Narmada

  公开号：US06878733B1

  公开（公告）日：2005-04-12

  The present invention features formulations of indolinones which compounds are ionizable as free acids or free bases. The formulation is suitable for parenteral or oral administration, wherein the formulation comprises an ionizable substituted indolinone, and a pharmaceutically acceptable carrier therefor. The term “ionizable substituted indolinone” includes pyrrole substituted 2-indolinones which, in addition to being otherwise optionally substituted on both the pyrrole and 2-indolinone portions of the compound, are necessarily substituted on the pyrrole moiety with one or more hydrocarbon chains which themselves are substituted with at least one polar group. The formulations and the compounds themselves are useful for the treatment of protein kinase related disorders as discussed herein.

  本发明涉及吲哚酮的配方，这些化合物作为游离酸或游离碱是可离子化的。该配方适用于静脉或口服给药，其中配方包括可离子化的取代吲哚酮和其药用可接受载体。术语“可离子化的取代吲哚酮”包括吡咯取代的2-吲哚酮，除了在化合物的吡咯和2-吲哚酮部分上可选择地被取代外，必须在吡咯基上用一个或多个烃链取代，这些烃链本身被至少一个极性基团取代。如本文所述，这些配方和化合物本身对于治疗蛋白激酶相关疾病是有用的。
• A Unified Catalytic Asymmetric (4+1) and (5+1) Annulation Strategy to Access Chiral Spirooxindole‐Fused Oxacycles
  作者：Min Gao、Yanshu Luo、Qianlan Xu、Yukun Zhao、Xiangnan Gong、Yuanzhi Xia、Lin Hu

  DOI：10.1002/anie.202105282

  日期：2021.9

  A unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides has been achieved in the presence of a chiral phase-transfer catalyst (PTC). This general strategy utilizes peroxides as unique bielectrophilic four- or five-atom synthons to participate in the C−C and the subsequent umpolung C−O bond-forming reactions with one-carbon unit nucleophiles, thus providing

  在手性相转移催化剂 (PTC) 的存在下，已经实现了羟吲哚与双官能过氧化物的统一催化不对称 ( N +1) ( N =4, 5) 环化反应。这种通用策略利用过氧化物作为独特的双亲电四原子或五原子合成子参与 C−C 和随后与单碳单元亲核试剂的 umpolung C−O 键形成反应，从而提供了一种独特的方法来获得有价值的手性螺吲哚-四氢呋喃和-四氢吡喃在温和条件下具有良好的产率和高对映选择性。进行 DFT 计算以合理化高对映选择性的起源。还证明了所得产物的克级合成和合成效用。