3-(5-fluoro-2-methyl-1H-inden-3-yl)propanenitrile | 54215-59-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: 3-(5-fluoro-2-methyl-1H-inden-3-yl)propanenitrile
• 英文别名: 3-(6-fluoro-2-methyl-3H-inden-1-yl)propanenitrile
• CAS: 54215-59-7
• 化学式: C₁₃H₁₂FN
• 分子量: 201.243
• InChiKey: HZOAUUIADMPEIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(5-fluoro-2-methyl-1H-inden-3-yl)propanenitrile 、 4-异丙基苯甲醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 4.5h， 以53%的产率得到(Z)-3-(5-fluoro-1-(4-isopropylbenzylidene)-2-methyl-1H-inden-3-yl)propanenitrile
  参考文献：
  名称：

  [EN] METHODS AND COMPOSITIONS FOR TREATING CANCER
  [FR] MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT DU CANCER

  摘要：

  本文提供的实施例涉及用于治疗癌症的方法和组合物。一些实施例涉及具有对视黄醇X受体-α（RXRa）活性的某些化合物。一些实施例包括设计或识别结合到人类RXRa蛋白的化合物，例如人类RXRa蛋白的配体结合结构域（LBD）。

  公开号：

  WO2015100267A1
• 作为产物：
  描述：

  6-氟-2-甲基-1-茚酮 在 硫酸 、 溶剂黄146 、 异丙醇 作用下， 以 四氢呋喃 为溶剂， 反应 4.41h， 生成 3-(5-fluoro-2-methyl-1H-inden-3-yl)propanenitrile
  参考文献：
  名称：

  Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation

  摘要：

  RXR alpha represents an intriguing and unique target for pharmacologic interventions. We recently showed that Sulindac and a designed analog could bind to RXR alpha and modulate its biological activity, including inhibition of the interaction of an N-terminally truncated RXR alpha (tRXR alpha) with the p85 alpha regulatory subunit of phosphatidylinositol-3-OH kinase (PI3K). Here we report the synthesis, testing and SAR of a series of novel analogs of Sulindac as potential modulators for inhibiting tRXR alpha-dependent AKT activation. A new compound 30 was identified to have improved biological activity. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.012

文献信息

• Sulindac-Derived RXRα Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site
  作者：Liqun Chen、Zhi-Gang Wang、Alexander E. Aleshin、Fan Chen、Jiebo Chen、Fuquan Jiang、Gulimiran Alitongbieke、Zhiping Zeng、Yue Ma、Mingfeng Huang、Hu Zhou、Gregory Cadwell、Jian-Feng Zheng、Pei-Qiang Huang、Robert C. Liddington、Xiao-kun Zhang、Ying Su

  DOI：10.1016/j.chembiol.2014.02.017

  日期：2014.5

  Retinoid X receptor-alpha (RXR alpha), an intriguing and unique drug target, can serve as an intracellular target mediating the anticancer effects of certain nonsteroidal anti-inflammatory drugs (NSAIDs), including sulindac. We report the synthesis and characterization of two sulindac analogs, K-8008 and K-8012, which exert improved anticancer activities over sulindac in a RXR alpha-dependent manner. The analogs inhibit the interaction of the N-terminally truncated RXR alpha (tRXR alpha) with the p85 alpha subunit of PI3K, leading to suppression of AKT activation and induction of apoptosis. Crystal structures of the RXR alpha ligand-binding domain (LBD) with K-8008 or K-8012 reveal that both compounds bind to tetrameric RXR alpha LBD at a site different from the classical ligand-binding pocket. Thus, these results identify K-8008 and K-8012 as tRXR alpha modulators and define a binding mechanism for regulating the nongenomic action of tRXR alpha.
• Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation
  作者：Zhi-Gang Wang、Liqun Chen、Jiebo Chen、Jian-Feng Zheng、Weiwei Gao、Zhiping Zeng、Hu Zhou、Xiao-kun Zhang、Pei-Qiang Huang、Ying Su

  DOI：10.1016/j.ejmech.2013.01.012

  日期：2013.4

  RXR alpha represents an intriguing and unique target for pharmacologic interventions. We recently showed that Sulindac and a designed analog could bind to RXR alpha and modulate its biological activity, including inhibition of the interaction of an N-terminally truncated RXR alpha (tRXR alpha) with the p85 alpha regulatory subunit of phosphatidylinositol-3-OH kinase (PI3K). Here we report the synthesis, testing and SAR of a series of novel analogs of Sulindac as potential modulators for inhibiting tRXR alpha-dependent AKT activation. A new compound 30 was identified to have improved biological activity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• [EN] METHODS AND COMPOSITIONS FOR TREATING CANCER<br/>[FR] MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT DU CANCER
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2015100267A1

  公开（公告）日：2015-07-02

  Embodiments provided herein relate to methods and compositions for treating cancer. Some embodiments relate to certain compounds having activity against retinoid X receptor-alpha (RXRa). Some embodiments included designing or identifying a compound that binds to human RXRa protein, such as the ligand binding domain (LBD) of human RXRa protein.

  本文提供的实施例涉及用于治疗癌症的方法和组合物。一些实施例涉及具有对视黄醇X受体-α（RXRa）活性的某些化合物。一些实施例包括设计或识别结合到人类RXRa蛋白的化合物，例如人类RXRa蛋白的配体结合结构域（LBD）。