2-(3-(5-(3,4-dimethoxyphenyl)-1-oxoisoindolin-2-yl)phenyl)acetonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(3-(5-(3,4-dimethoxyphenyl)-1-oxoisoindolin-2-yl)phenyl)acetonitrile
• 英文别名: 2-[3-[6-(3,4-dimethoxyphenyl)-3-oxo-1H-isoindol-2-yl]phenyl]acetonitrile
• 化学式: C₂₄H₂₀N₂O₃
• 分子量: 384.434
• InChiKey: BLJYMHUQTWGYDK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴-2-溴甲基苯甲酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 caesium carbonate 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.59h， 生成 2-(3-(5-(3,4-dimethoxyphenyl)-1-oxoisoindolin-2-yl)phenyl)acetonitrile
  参考文献：
  名称：

  Design and Synthesis of a Novel Series of Orally Bioavailable, CNS-Penetrant, Isoform Selective Phosphoinositide 3-Kinase γ (PI3Kγ) Inhibitors with Potential for the Treatment of Multiple Sclerosis (MS)

  摘要：

  The lipid kinase phosphoinositide 3-kinase gamma (PI3K gamma) has attracted attention as a potential target to treat a variety of autoimmune disorders, including multiple sclerosis, due to its role in immune modulation and microglial activation. By minimizing the number of hydrogen bond donors while targeting a previously uncovered selectivity pocket adjacent to the ATP binding site of PI3K gamma, we discovered a series of aza-isoindolinones as selective, brain penetrant inhibitors of PI3K gamma. This ultimately led to the discovery of 16, an orally bioavailable compound that showed efficacy murine experimental autoimmune encephalomyelitis (EAE), a preclinical model of multiple sclerosis.

  DOI：

  10.1021/acs.jmedchem.8b00085