5-Acetylaminoindirubin | 910035-28-8

• 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: 5-Acetylaminoindirubin
• 英文别名: N-[(3Z)-2-oxo-3-(3-oxo-1H-indol-2-ylidene)-1H-indol-5-yl]acetamide
• CAS: 910035-28-8
• 化学式: C₁₈H₁₃N₃O₃
• 分子量: 319.32
• InChiKey: MNKJDIFJOOLBQY-NXVVXOECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.62
• 重原子数：
  24.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  87.3
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  5-Acetylaminoindirubin 在 吡啶 、 盐酸羟胺 作用下， 生成 5-(acetylamino)indirubin-3'-oxime
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities

  摘要：

  Indirubin, an active ingredient of a traditional Chinese recipe Danggui Loughui Wan, has been known as it CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/ threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, Such its alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group Containing acylamino Substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, Which resulted in the discovery of potent CDK2 inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.008
• 作为产物：
  描述：

  吲哚乙酸酯 在 吡啶 、 sodium carbonate 、 tin(ll) chloride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 5-Acetylaminoindirubin
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities

  摘要：

  Indirubin, an active ingredient of a traditional Chinese recipe Danggui Loughui Wan, has been known as it CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/ threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, Such its alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group Containing acylamino Substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, Which resulted in the discovery of potent CDK2 inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.08.008

文献信息

• Indigoid bisindole derivatives
  申请人：Faustus Forschungs Cie. Translational Cancer Research GmbH

  公开号：US06987092B1

  公开（公告）日：2006-01-17

  The present invention relates to novel indigoid binsindole derivatives which can be used for the manufacture of a medicament for the treatment of solid cancers.

  本发明涉及一种新型吲哚蓝类二氮烷衍生物，可用于制造用于治疗实体癌症的药物。
• Synthesis and kinase inhibitory activity of novel substituted indigoids
  作者：Anne Beauchard、Hélène Laborie、Hervé Rouillard、Olivier Lozach、Yoan Ferandin、Rémy Le Guével、Christiane Guguen-Guillouzo、Laurent Meijer、Thierry Besson、Valérie Thiéry

  DOI：10.1016/j.bmc.2009.07.051

  日期：2009.9.1

  The bis-indole indigoids are a promising protein kinase inhibitor scaffold to be further evaluated against the numerous human diseases that imply abnormal regulation of kinases including neurodegenerative disorders. In an effort to identify new pharmacological inhibitors of disease-relevant protein kinases with increased potency and selectivity, we designed, synthesized new 5,7-disubstituted or 6-substituted bis-indole derivatives. On the basis of our previous synthetic work, 22 selected compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3 alpha/beta kinases, five kinases involved in Alzheimer's disease. Some of them were also evaluated for their cytotoxic and antiproliferative activities. 6-Nitro-3'-N-oxime-indirubin and 5-amino-3'- N-oxime-indirubin derivatives exhibited inhibitory activity in a submicromolar range against CDK1/cyclin B (0.18 and 0.1 mu M, respectively), CK1 (0.6 mu M and 0.13 mu M) and GSK3 (0.04 mu M and 0.36 mu M). (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of novel 5-substituted indirubins as protein kinases inhibitors
  作者：A BEAUCHARD、Y FERANDIN、S FRERE、O LOZACH、M BLAIRVACQ、L MEIJER、V THIERY、T BESSON

  DOI：10.1016/j.bmc.2006.05.036

  日期：2006.9.15

  In an effort to identify new pharmacological inhibitors of disease-relevant protein kinases with increased potency and selectivity, we synthesized and evaluated new 5-substituted indirubins. The effects of 34 indirubin derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3, as well as on SH-SY5Y human neuroblastoma cell survival, were investigated. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities
  作者：Myoung Ju Moon、Sang Kook Lee、Jong-Won Lee、Woo Keun Song、Si Wouk Kim、Jae Il Kim、Chunghee Cho、Soo Jeong Choi、Yong-Chul Kim

  DOI：10.1016/j.bmc.2005.08.008

  日期：2006.1

  Indirubin, an active ingredient of a traditional Chinese recipe Danggui Loughui Wan, has been known as it CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/ threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, Such its alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group Containing acylamino Substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, Which resulted in the discovery of potent CDK2 inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.