N-(3-Bromo-4-methylphenyl)-2-(hydroxyimino)acetamide | 147149-83-5

• 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: N-(3-Bromo-4-methylphenyl)-2-(hydroxyimino)acetamide
• 英文别名: N-(3-bromo-4-methylphenyl)-2-hydroxyiminoacetamide
• CAS: 147149-83-5
• 化学式: C₉H₉BrN₂O₂
• 分子量: 257.087
• InChiKey: LEQIRJQMGCGTSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-Bromo-4-methylphenyl)-2-(hydroxyimino)acetamide 在 吡啶 、 硫酸 、 盐酸羟胺 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 5.25h， 生成 6-Bromo-5-methylindirubin-3'-acetoxime
  参考文献：
  名称：

  Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases

  摘要：

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.

  DOI：

  10.1021/jm031016d
• 作为产物：
  描述：

  3-溴-4-甲基苯胺 以76的产率得到N-(3-Bromo-4-methylphenyl)-2-(hydroxyimino)acetamide
  参考文献：
  名称：

  [EN] ANTIPROLIFERATIVE QUINAZOLINES
  [FR] QUINAZOLINES ANTI-PROLIFERATIVES

  摘要：

  (中) 描述了一种表现出抗增殖活性，如抗肿瘤活性的喹唑啉化合物，以及制备这些化合物的过程，含有这些化合物的药物组合物，以及这些化合物的用途。这些化合物抑制高等生物和微生物（如细菌，酵母菌和真菌）的细胞生长和增殖。优选的喹唑啉化合物能够抑制胸腺嘧啶合成酶酶。由抑制胸腺嘧啶合成酶酶产生的效应包括上述讨论的效应。

  公开号：

  WO1993020055A1

文献信息

• J. Med. Chem. 1993, 36, 733-746
  作者：

  DOI：——

  日期：——
• Chemical Reagents 2011, 33, 1131-1134
  作者：

  DOI：——

  日期：——
• Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases
  作者：Panagiotis Polychronopoulos、Prokopios Magiatis、Alexios-Leandros Skaltsounis、Vassilios Myrianthopoulos、Emmanuel Mikros、Aldo Tarricone、Andrea Musacchio、S. Mark Roe、Laurence Pearl、Maryse Leost、Paul Greengard、Laurent Meijer

  DOI：10.1021/jm031016d

  日期：2004.2.1

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.
• [EN] ANTIPROLIFERATIVE QUINAZOLINES<br/>[FR] QUINAZOLINES ANTI-PROLIFERATIVES
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：WO1993020055A1

  公开（公告）日：1993-10-14

  (EN) Quinazoline compounds which demonstrate antiproliferative activity, such as antitumor activity, processes of preparing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds. These compounds inhibit the growth and proliferation of the cells of higher organisms and microorganisms, such as bacteria, yeasts and fungi. Preferred quinazoline compounds are capable of inhibiting the enzyme thymidylate synthase. Effects derived from the inhibition of the enzyme thymidylate synthase include those discussed above.(FR) On décrit des composés de quinazoline qui manifestent une activité anti-proliférative telle qu'une activité anti-tumorale, des procédés permettant de préparer ces composés, des compositions pharmaceutiques qui les contiennent, ainsi que l'utilisation desdits composés. Ces derniers inhibent la croissance et la prolifération de cellules chez les organismes supérieurs et les micro-organismes tels que les bactéries, les levures et les champignons. Des composés de quinazoline préférés sont en mesure d'inhiber une enzyme, la thymidylate synthase. Les effets provenant de cette inhibition de la thymidylate synthase incluent ceux mentionnés ci-dessus.

  (中) 描述了一种表现出抗增殖活性，如抗肿瘤活性的喹唑啉化合物，以及制备这些化合物的过程，含有这些化合物的药物组合物，以及这些化合物的用途。这些化合物抑制高等生物和微生物（如细菌，酵母菌和真菌）的细胞生长和增殖。优选的喹唑啉化合物能够抑制胸腺嘧啶合成酶酶。由抑制胸腺嘧啶合成酶酶产生的效应包括上述讨论的效应。