3-[6-Fluoro-2-methyl-3-[(4-propan-2-ylphenyl)methylidene]inden-1-yl]propanenitrile | 1632470-63-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 3-[6-Fluoro-2-methyl-3-[(4-propan-2-ylphenyl)methylidene]inden-1-yl]propanenitrile
• CAS: 1632470-63-3
• 化学式: C₂₃H₂₂FN
• 分子量: 331.433
• InChiKey: UYMXXTSSNXITPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 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-[6-Fluoro-2-methyl-3-[(4-propan-2-ylphenyl)methylidene]inden-1-yl]propanenitrile 在 sodium azide 、 三乙胺盐酸盐 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 K-8012
  参考文献：
  名称：

  Sulindac-Derived RXRα Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site

  摘要：

  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.

  DOI：

  10.1016/j.chembiol.2014.02.017
• 作为产物：
  描述：

  在 硫酸 、 sodium methylate 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 3-[6-Fluoro-2-methyl-3-[(4-propan-2-ylphenyl)methylidene]inden-1-yl]propanenitrile
  参考文献：
  名称：

  Sulindac-Derived RXRα Modulators Inhibit Cancer Cell Growth by Binding to a Novel Site

  摘要：

  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.

  DOI：

  10.1016/j.chembiol.2014.02.017

文献信息

• METHODS AND COMPOSITIONS FOR TREATING CANCER
  申请人：Su Ying

  公开号：US20160340324A1

  公开（公告）日：2016-11-24

  Embodiments provided herein relate to methods and compositions for treating cancer. Some embodiments relate to certain compounds having activity against retinoid X receptor-alpha (RXRα). 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.