2-amino-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-amino-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• 化学式: C₁₃H₉N₅
• 分子量: 235.248
• InChiKey: AIGCPZYQUFVGJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-氧代-4,7-二氢-3H-吡咯并[2,3-D]嘧啶-5-甲腈 在 吡啶 、 四(三苯基膦)钯 、 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 叔丁胺 、 三氯氧磷 作用下， 以 水 、 异丙醇 、 乙腈 为溶剂， 反应 23.67h， 生成 2-amino-4-phenyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
  参考文献：
  名称：

  Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers

  摘要：

  IKK beta plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKK alpha in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKK beta, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKK alpha over IKK beta. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKK alpha. We demonstrate effective target engagement and selectivity with IKK alpha in U2OS cells through inhibition of IKK alpha-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKK beta-dependent IKapp-B alpha loss in the canonical pathway. These compounds represent the first chemical tools that can be used to further characterize the role of IKK alpha a in cellular signaling, to dissect this from IKK beta and to validate it in its own right as a target in inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.7b00484