5-bromo-3-hydroxy-2-methoxy-3-phenylisoindolin-1-one | 1456693-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 5-bromo-3-hydroxy-2-methoxy-3-phenylisoindolin-1-one
• 英文别名: 5-Bromo-3-hydroxy-2-methoxy-3-phenylisoindol-1-one
• CAS: 1456693-87-0
• 化学式: C₁₅H₁₂BrNO₃
• 分子量: 334.169
• InChiKey: YTRQJFYKMKOZGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,5-二甲基异恶唑-4-硼酸频哪醇酯 、 5-bromo-3-hydroxy-2-methoxy-3-phenylisoindolin-1-one 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 以72 %的产率得到5-(3, 5-dimethylisoxazol-4-yl)-3-hydroxy-2-methoxy-3-phenylisoindolin-1-one
  参考文献：
  名称：

  Stable and Reusable Pd/Cu Bimetallic Nanoparticle Catalysts for the Synthesis of Hydroxy Isoindolones by Domino C−H Activation and Annulation

  摘要：

  A stable and reusable bimetallic nanoparticles (Pd/Cu‐Binapthyl Nanoparticles) catalyzed synthesis of 3‐hydroxyisoindolin‐1‐ones/thiones has been developed using domino C‐H activation and annulation. The reaction's scope was examined utilizing a variety of N‐alkoxy benzamide/benzothioamide derivatives and benzaldehydes, which yielded moderate to good yields of 3‐hydroxyisoindolin‐1‐ones/thiones, one of which was used to synthesize the BRD4 inhibitor. A gram‐scale synthesis is added to the model reaction. The Pd/Cu‐ Binapthyl nanocatalyst has been recovered and reused up to four times without any major change in particle size and reactivity.  

  DOI：

  10.1002/ejoc.202400471
• 作为产物：
  描述：

  4-溴苯甲酰氯 在 叔丁基过氧化氢 、 palladium diacetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 4.25h， 生成 5-bromo-3-hydroxy-2-methoxy-3-phenylisoindolin-1-one
  参考文献：
  名称：

  Pd介导的C ？高效合成羟基异吲哚酮 H活化/环化反应

  摘要：

  自由基反应：通过Pd催化的CH活化/环化反应，以接近“点击化学”的效率，可以方便地合成羟基异吲哚酮（见方案； TBHP =叔丁基过氧化氢）。该方法的特点是反应时间短（10-30分钟），原子经济性高，底物范围广（22个实例），反应产率高（高达93％）。

  DOI：

  10.1002/chem.201302031

文献信息

• 3-Hydroxyisoindolin-1-one derivates: Synthesis by palladium-catalyzed C H activation as BRD4 inhibitors against human acute myeloid leukemia (AML) cells
  作者：Pan Chen、Yifei Yang、Lingyun Yang、Jiping Tian、Fangqing Zhang、Jinpei Zhou、Huibin Zhang

  DOI：10.1016/j.bioorg.2019.01.034

  日期：2019.5

  Bromodomain protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) protein family, which plays a key role in transcriptional regulation. Recent biological and pharmacological studies have enabled linking of the BET bromodomains with diseases, including inflammation and cancer, suggesting that bromodomains are druggable targets. In this study, we made further structural modifications of our previously reported BRD4 inhibitors, to develop new chemical scaffold 3-Hydroxyisoindolin-1-One. Then a series of compounds (10a-q) were synthesized via palladium-catalyzed C-H activation and BRD4-inhibitory activities and anti-proliferative effects of these compounds were evaluated. Compound 10e exhibited excellent BRD4-inhibitory activity with IC50 value of 80 nM and anti-proliferation potency with IC50 value of 365 nM in HL-60 (human promyelocytic leukemia) cancer cell lines. We have demonstrated compound 10e modulated the intrinsic apoptotic pathway. In conclusion, these results suggested that compound 10e could be utilized as a BRD4 inhibitor for further leukemia treatment.