(3Z)-5-chloro-3-(5-Chloro-1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,3-dihydro-2H-indol-2-one | 1223386-27-3

• 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: (3Z)-5-chloro-3-(5-Chloro-1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,3-dihydro-2H-indol-2-one
• 英文别名: (2'Z)-5,5'-dichloroindirubin；(2Z)-5-chloro-2-(5-chloro-2-oxo-1H-indol-3-ylidene)-1H-indol-3-one
• CAS: 1223386-27-3
• 化学式: C₁₆H₈Cl₂N₂O₂
• 分子量: 331.158
• InChiKey: STCKUKJICYDGAK-YPKPFQOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  22.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3Z)-5-chloro-3-(5-Chloro-1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,3-dihydro-2H-indol-2-one 在 盐酸羟胺 作用下， 以 吡啶 为溶剂， 反应 2.0h， 生成 (2'Z,3'E)-5-chloro-5'-chloro-indirubin-3'-oxime
  参考文献：
  名称：

  5,5′-Substituted Indirubin-3′-oxime Derivatives as Potent Cyclin-Dependent Kinase Inhibitors with Anticancer Activity

  摘要：

  To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3'-oxime derivatives with combined substitutions at the 5 and 5' positions. A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5' position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Among the synthesized derivatives, the 5-nitro-5'-hydroxy analogue 3a and the 5-nitro-5'-fluoro analogue Sa displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. These derivatives also showed antiproliferative activity against several human cancer cell lines, with IC(50) values of 0.2-3.3 mu M. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity.

  DOI：

  10.1021/jm100080z
• 作为产物：
  描述：

  5-氯靛红 在 钾硼氢 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以83.6%的产率得到(3Z)-5-chloro-3-(5-Chloro-1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,3-dihydro-2H-indol-2-one
  参考文献：
  名称：

  靛红与KBH 4的还原偶联一步合成靛玉红

  摘要：

  描述了通过Isatin与KBH 4的还原偶联一步一步合成天然产物靛玉红的方法，并提出了可能的反应机理。从相应的取代的靛红很容易获得11种靛玉红衍生物。

  DOI：

  10.1016/j.tet.2017.03.077

文献信息

• Improved Synthesis of Indirubin Derivatives by Sequential Build-Up of the Indoxyl Unit: First Preparation of Fluorescent Indirubins
  作者：Herbert M. Riepl、Corinna Urmann

  DOI：10.1002/hlca.201200042

  日期：2012.8

  synthesis of its derivatives relies on the combination of isatins and 2,3‐dihydro‐1H‐indol‐3‐one (‘indoxyl’) derivatives and usually yields indigo as well as other by‐products. Inspection of the hydrolysis of the long‐known condensation products of 2‐thioxothiazolidin‐4‐one with isatins gave useful hints for an improved synthesis of indirubins: this reaction does not yield quinoline derivatives but 2‐(2,

  靛玉红，存在于提取物板蓝根和其它一些植物物种，有希望的细胞毒性对通过抑制细胞周期蛋白依赖性激酶的多种细胞系。其衍生物的化学合成依赖于靛红和2,3-二氢-1 H-吲哚-3-酮（'indoxyl'）衍生物的组合，通常会产生靛蓝以及其他副产物。检查2-硫代噻唑并恶唑啉-4-酮与靛红的长期缩合产物的水解，为改善靛玉红的合成提供了有用的提示：此反应不会产生喹啉衍生物，但会生成2-（2,3-二氢-2-酮氧代1 H吲哚3亚基）2硫烷基乙酸。通过用苯胺取代该羟吲哚中的硫烷基，并在室温下直接环化因此，在纳扎罗夫条件下，通常可以以很高的纯度和收率得到在吲哚环系统中取代的各种靛玉红。在这个反应顺序使用萘胺的产生的各种荧光物质用λ FL在约 630纳米
• INDIRUBIN-3'-OXIME DERIVATIVES AS POTENT CYCLIN DEPENDENT KINASE INHIBITORS
  申请人：Kim Yong-Chul

  公开号：US20120295948A1

  公开（公告）日：2012-11-22

  The present invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor with anti-cancer activity. More particularly, this invention relates to an indirubin-3′-oxime derivative as potent cyclin dependent kinase inhibitor having excellent anti-cancer activity against human lung cancer cell, human fibro sarcoma cell, human colon cancer cell, human leukemia cell, human stomach cancer cell, human nasopharyngeal cancer cell and/or human breast cancer cell.

  本发明涉及一种indirubin-3'-oxime衍生物，作为强效的细胞周期蛋白依赖性激酶抑制剂，具有抗癌活性。更具体地说，本发明涉及一种indirubin-3'-oxime衍生物，作为强效的细胞周期蛋白依赖性激酶抑制剂，对人肺癌细胞、人纤维肉瘤细胞、人结肠癌细胞、人白血病细胞、人胃癌细胞、人鼻咽癌细胞和/或人乳腺癌细胞具有优异的抗癌活性。
• US8859783B2
  申请人：——

  公开号：US8859783B2

  公开（公告）日：2014-10-14
• One step synthesis of indirubins by reductive coupling of isatins with KBH 4
  作者：Cuiling Wang、Jiaxu Yan、Mo Du、Joseph A. Burlison、Chi Li、Yanni Sun、Danqing Zhao、Jianli Liu

  DOI：10.1016/j.tet.2017.03.077

  日期：2017.5

  One step synthesis of the natural product indirubin by reductive coupling of isatin with KBH4 is described and a possible mechanism for the reaction is proposed. Eleven indirubin derivatives were obtained easily from the corresponding substituted isatin.

  描述了通过Isatin与KBH 4的还原偶联一步一步合成天然产物靛玉红的方法，并提出了可能的反应机理。从相应的取代的靛红很容易获得11种靛玉红衍生物。
• 5,5′-Substituted Indirubin-3′-oxime Derivatives as Potent Cyclin-Dependent Kinase Inhibitors with Anticancer Activity
  作者：Soo-Jeong Choi、Jung-Eun Lee、Soon-Young Jeong、Isak Im、So-Deok Lee、Eun-Jin Lee、Sang Kook Lee、Seong-Min Kwon、Sang-Gun Ahn、Jung-Hoon Yoon、Sun-Young Han、Jae-Il Kim、Yong-Chul Kim

  DOI：10.1021/jm100080z

  日期：2010.5.13

  To enhance the ability of indirubin derivatives to inhibit CDK2/cyclin E, a target of anticancer agents, we designed and synthesized a new series of indirubin-3'-oxime derivatives with combined substitutions at the 5 and 5' positions. A molecular docking study predicted the binding of derivatives with OH or halogen substitutions at the 5' position to the ATP binding site of CDK2, revealing the critical interactions that may explain the improved CDK2 inhibitory activity of these derivatives. Among the synthesized derivatives, the 5-nitro-5'-hydroxy analogue 3a and the 5-nitro-5'-fluoro analogue Sa displayed potent inhibitory activity against CDK2, with IC(50) values of 1.9 and 1.7 nM, respectively. These derivatives also showed antiproliferative activity against several human cancer cell lines, with IC(50) values of 0.2-3.3 mu M. A representative analogue, 3a, showed greater than 500-fold selectivity for CDK relative to selected kinase panel and potent in vivo anticancer activity.