2-氨基-4-羟基苯乙酮 | 90033-64-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-氨基-4-羟基苯乙酮
• 英文名称: 2-amino-4-hydroxyacetophenone
• 英文别名: 2-amino-4′-hydroxyacetophenone；1-(2-Amino-4-hydroxyphenyl)ethanone
• CAS: 90033-64-0
• 化学式: C₈H₉NO₂
• 分子量: 151.165
• InChiKey: YQSBOMDRAHLOEE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨基-4-羟基苯乙酮 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 25.0~200.0 ℃ 、206.84 kPa 条件下， 反应 28.0h， 生成 methyl 4-<(3-acetamido-4-acetyl-2-propylphenoxy)methyl>-3-methoxybenzoate
  参考文献：
  名称：

  Hydroxyacetophenone-derived antagonists of the peptidoleukotrienes

  摘要：

  Considerations of the possible similarities between leukotriene D4 and its prototypical antagonist, FPL 55712, led to the development of a new series of leukotriene antagonists incorporating a hydroxyacetophenone group (e.g., the toluic acids 16 and 18). Although considerable attention has focused on FPL 55712-derived analogues, only limited investigations into alternatives for the standard 4-acetyl-3-hydroxy-2-propylphenoxy moiety have been reported. Therefore, an extensive study of modifications to the hydroxyacetophenone portion of toluic acid 18 was undertaken. Although no viable alternative to the 3-hydroxy moiety was discovered, replacements for the 2-propyl group (34, 37) and the 4-acetyl functionality (56, 59) yielded potent antagonists. A number of compounds exhibited longer duration of action in vivo than FPL 55712.

  DOI：

  10.1021/jm00124a014
• 作为产物：
  描述：

  2’-氨基-4’-甲氧基苯乙酮 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 以63%的产率得到2-氨基-4-羟基苯乙酮
  参考文献：
  名称：

  Hydroxyacetophenone-derived antagonists of the peptidoleukotrienes

  摘要：

  Considerations of the possible similarities between leukotriene D4 and its prototypical antagonist, FPL 55712, led to the development of a new series of leukotriene antagonists incorporating a hydroxyacetophenone group (e.g., the toluic acids 16 and 18). Although considerable attention has focused on FPL 55712-derived analogues, only limited investigations into alternatives for the standard 4-acetyl-3-hydroxy-2-propylphenoxy moiety have been reported. Therefore, an extensive study of modifications to the hydroxyacetophenone portion of toluic acid 18 was undertaken. Although no viable alternative to the 3-hydroxy moiety was discovered, replacements for the 2-propyl group (34, 37) and the 4-acetyl functionality (56, 59) yielded potent antagonists. A number of compounds exhibited longer duration of action in vivo than FPL 55712.

  DOI：

  10.1021/jm00124a014

文献信息

• [EN] AURISTATIN DERIVATIVES AND CONJUGATES THEREOF<br/>[FR] DÉRIVÉS D'AURISTATINE ET CONJUGUÉS DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2015189791A1

  公开（公告）日：2015-12-17

  Disclosed herein are novel compounds of formula (I) as described herein, and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel compound linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

  本文披露了如下所述的化合物(I)的新颖化合物，以及在制备免疫结合物（即抗体药物结合物）中使用这些肽的用途。本文还描述了包括这种新颖化合物与抗原结合基团（如抗体）连接的免疫结合物（即抗体药物结合物），这些免疫结合物可用于治疗细胞增殖性疾病。该发明还提供了包括这些免疫结合物的药物组合物，包括与治疗性辅助剂一起的免疫结合物的组合物，以及使用这些免疫结合物和组合物治疗细胞增殖性疾病的方法。
• [EN] ANTIBODY CONJUGATES COMPRISING TOLL-LIKE RECEPTOR AGONIST<br/>[FR] CONJUGUÉS D'ANTICORPS COMPRENANT UN AGONISTE DU RÉCEPTEUR DE TYPE TOLL
  申请人：NOVARTIS AG

  公开号：WO2017072662A1

  公开（公告）日：2017-05-04

  Provided herein are antibody conjugates comprising toll-like receptor agonists and the use of such conjugates for the treatment of cancer. In some embodiments, the conjugates comprise anti-HER2 antibodies.

  本文提供了包含Toll样受体激动剂的抗体偶联物，以及利用这些偶联物治疗癌症的用途。在某些实施例中，这些偶联物包括抗HER2抗体。
• [EN] AMATOXIN DERIVATIVES AND CONJUGATES THEREOF AS INHIBITORS OF RNA POLYMERASE<br/>[FR] DÉRIVÉS D'AMATOXINE ET LEURS CONJUGUÉS COMME INHIBITEURS DE L'ARN POLYMÉRASE
  申请人：NOVARTIS AG

  公开号：WO2016071856A1

  公开（公告）日：2016-05-12

  The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (I), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates: Formula (I).

  本发明涉及一种公式（I）的细胞毒性环肽，使用这种环肽抑制RNA聚合酶的方法，包含这种环肽的免疫结合物（即抗体药物结合物），包含这种环肽免疫结合物的药物组合物，包含这种环肽免疫结合物和治疗辅助剂的组合物以及使用这种环肽免疫结合物进行治疗的方法：公式（I）。
• BIOSYNTHETICALLY GENERATED PYRROLINE-CARBOXY-LYSINE AND SITE SPECIFIC PROTEIN MODIFICATIONS VIA CHEMICAL DERIVATIZATION OF PYRROLINE-CARBOXY-LYSINE AND PYRROLYSINE RESIDUES
  申请人：GEIERSTANGER Bernhard

  公开号：US20140302553A1

  公开（公告）日：2014-10-09

  Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analogue, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

  本文披露了一种吡咯烷酸-半胱氨酸(PCL)，一种类似于吡咯赖氨酸的天然生物合成产生的氨基酸，并且披露了生物合成生成PCL的方法。本文还披露了具有PCL的蛋白质、多肽和肽的方法，并且披露了将PCL纳入这些蛋白质、多肽和肽中的方法。本文还披露了在具有PCL或吡咯赖氨酸的蛋白质、多肽和肽中进行位点特异性衍生化的方法。本文还披露了在具有PCL或吡咯赖氨酸的蛋白质、多肽和肽中进行交联的方法。
• A process for the preparation of ketones
  申请人：FINE ORGANICS LIMITED

  公开号：EP0431871A2

  公开（公告）日：1991-06-12

  The present invention relates to the preparation of aminoalkyl p-hydroxyphenyl ketones. Certain of these ketones are well known as important intermediates in the production of compounds having pharmaceutical activity, for example octopamine or synephrine. The known Houben-Hoesch reaction is a variation of the Friedel-Crafts reaction and involves the condensation of a phenolic substrate with a nitrile in the presence of a Lewis acid catalyst to give a hydroxy-aryl ketone. It is an object of the invention to provide a new or improved process for the manufacture of aminoalkyl p-hydroxyphenyl ketones. According to the invention, there is provided a process for the preparation of an aminoalkyl p-hydroxyphenyl ketone comprising reacting phenol with a nitrile, in the presence of a Lewis acid catalyst, to cause condensation thereof, the process being characterised in that the reaction is carried out in a medium comprising a nitroalkane solvent for the reactants. A preferred but non-limiting feature of the invention is the productiqn of 2'amino-4-hydroxyacetophenones. The present invention is based on the surprising discovery that nitroalkanes are unexpectedly much better solvents for this reaction, being less toxic, giving a better yield and also ensuring a homogeneous reaction medium. The nitroalkanes may also be diluted with a halogenated hydrocarbon solvent, which acts as an inert diluent, thus reducing the amount of nitroalkane used, and making the reaction less hazardous.

  本发明涉及氨基烷基对羟基苯基酮的制备。众所周知，其中某些酮类是生产具有药用活性的化合物（如辛胺或合肾上腺素）的重要中间体。 已知的 Houben-Hoesch 反应是 Friedel-Crafts 反应的一种变体，包括在路易斯酸催化剂存在下，酚类底物与腈缩合生成羟基芳基酮。 本发明的目的是提供一种制造氨基烷基对羟基苯基酮的新工艺或改进工艺。 根据本发明，提供了一种制备氨基烷基对羟基苯基酮的工艺，该工艺包括在路易斯酸催化剂存在下，使苯酚与腈反应以引起其缩合，该工艺的特征在于反应是在包括反应物的硝基烷烃溶剂的介质中进行的。 本发明的一个优选但非限制性特征是 2'氨基-4-羟基苯乙酮的产物。 本发明基于一个惊人的发现，即硝基烷烃是意想不到的更好的溶剂，毒性更低，产率更高，还能确保反应介质的均匀性。硝基烷烃还可以用卤代烃溶剂稀释，卤代烃溶剂可以作为惰性稀释剂，从而减少硝基烷烃的用量，降低反应的危险性。