(2'Z-3'E)-6-bromoindirubin-3'-[O-(2-hydroxyethyl)oxime] | 1067884-36-9

• 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: (2'Z-3'E)-6-bromoindirubin-3'-[O-(2-hydroxyethyl)oxime]
• CAS: 1067884-36-9
• 化学式: C₁₈H₁₄BrN₃O₃
• 分子量: 400.231
• InChiKey: CTJPHGZAOWJUHT-HPBPSMLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.95
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  2-溴乙醇 、 (2'Z,3'E)-6-溴靛玉红-3'-肟 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 以96%的产率得到(2'Z-3'E)-6-bromoindirubin-3'-[O-(2-hydroxyethyl)oxime]
  参考文献：
  名称：

  Soluble 3′,6-Substituted Indirubins with Enhanced Selectivity toward Glycogen Synthase Kinase -3 Alter Circadian Period

  摘要：

  Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective as GSK-3 inhibitors, most indirubins exhibit low water solubility. To address the issue of solubility, we have designed novel analogues of 6-bromo-indirubin-3'-oxime with increased hydrophilicity based on the GSK-3/indirubins cocrystal structures. The new derivatives with an extended amino side chain attached at position 3' showed potent GSK-3 inhibitory activity, enhanced selectivity, and dramatically increased water solubility. Furthermore, some of them displayed little or no cytotoxicity. The new indirubins inhibit GSK-3 in a cellular reporter model. They alter the circadian period measured in rhythmically expressing cell cultures, suggesting that they might constitute tools to investigate circadian rhythm regulation.

  DOI：

  10.1021/jm800648y

文献信息

• Indirubin Core Structure of Glycogen Synthase Kinase-3 Inhibitors as Novel Chemotype for Intervention with 5-Lipoxygenase
  作者：Carlo Pergola、Nicolas Gaboriaud-Kolar、Nadine Jestädt、Stefanie König、Marina Kritsanida、Anja M. Schaible、Haokun Li、Ulrike Garscha、Christina Weinigel、Dagmar Barz、Kai F. Albring、Otmar Huber、Alexios L. Skaltsounis、Oliver Werz

  DOI：10.1021/jm401740w

  日期：2014.5.8

  The enzymes 5-lipoxygenase (5-LO) and glycogen synthase kinase (GSK)-3 represent promising drug targets in inflammation. We made use of the bisindole core of indirubin, present in GSK-3 inhibitors, to innovatively target 5-LO at the ATP-binding site for the design of dual 5-LO/GSK-3 inhibitors. Evaluation of substituted indirubin derivatives led to the identification of (3Z)-6-bromo-3-[(3E)-3-hydroxyiminoindolin-2-ylidene]indolin-2-one (15) as a potent, direct, and reversible 5-LO inhibitor (IC50 = 1.5 mu M), with comparable cellular effectiveness on 5-LO and GSK-3. Together, we present indirubins as novel chemotypes for the development of 5-LO inhibitors, the interference with the ATP-binding site as a novel strategy for 5-LO targeting, and dual 5-LO/GSK-3 inhibition as an unconventional and promising concept for anti-inflammatory intervention.
• 3', 6-substituted indirubins and their biological applications
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2149553B1

  公开（公告）日：2011-10-19
• 3',6-SUBSTITUTED INDIRUBINS AND THEIR BIOLOGICAL APPLICATIONS
  申请人：Meijer Laurent

  公开号：US20110136808A1

  公开（公告）日：2011-06-09

  Indirubin derivatives of formula (I) wherein R represents -(A) n - R 1 or —CO—N(R 2 ,R 3 ) with •A being C1-C5 alkylene group, optionally substituted by one or several A 1 radical, A 1 being an halogen Br, OH, OR 4 or NH 2 , R 4 being C1-C5 alkyl; —R 1 being halogen, OH, N(R 2 , R 3 ); R 2 and R 3 , identical or different, being C1-C5 alkyl, optionally substituted by A 1 such as above defined, or R 2 and R 3 are part of a cycle with 5 or 6 elements optionally comprising another heteroatom such as O or N; •n=1−5. It also relates to the biological application thereof.
• US8829203B2
  申请人：——

  公开号：US8829203B2

  公开（公告）日：2014-09-09
• [EN] 3',6-SUBSTITUTED INDIRUBINS AND THEIR BIOLOGICAL APPLICATIONS<br/>[FR] INDIRUBINES SUBSTITUÉES EN 3',6 ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2010013168A1

  公开（公告）日：2010-02-04

  Indirubin derivatives of formula (I) wherein R represents - (A)n- R1 or -CO-N(R2,R3) with • A being C1-C5 alkylene group, optionally substituted by one or several A1 radical, A1 being an halogen Br, OH, OR4 or NH2, R4 being C1-C5 alkyl; - R1 being halogen, OH, N(R2, R3); R2 and R3, identical or different, being C 1 -C5 alkyl, optionally substituted by A1 such as above defined, or R2 and R3 are part of a cycle with 5 or 6 elements optionally comprising another heteroatom such as O or N; • n = 1-5. It also relates to the biological application thereof.