3-(3-fluoro-6-((3S,5S)-3-isobutyl-5-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine monoformate salt | 1422207-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(3-fluoro-6-((3S,5S)-3-isobutyl-5-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine monoformate salt
• CAS: 1422207-11-1
• 化学式: CH₂O₂*C₂₀H₂₅FN₆
• 分子量: 414.483
• InChiKey: USPNIHDXNGHZNM-IODNYQNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.07
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  107.03
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  甲酸 、 3-(3,6-difluoropyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine 、 (2S)-2-isobutyl-6-methylpiperazine 在 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 1.0h， 以1%的产率得到3-[3-fluoro-6-[(3R,5S)-3-methyl-5-(2-methylpropyl)piperazin-1-yl]pyridin-2-yl]-2H-pyrazolo[3,4-b]pyridine
  参考文献：
  名称：

  Design and Optimization of Selective Protein Kinase C θ (PKCθ) Inhibitors for the Treatment of Autoimmune Diseases

  摘要：

  Protein kinase C theta (PKC theta) has a central role in T cell activation and survival; however, the dependency of T cell responses to the inhibition of this enzyme appears to be dictated by the nature of the antigen and by the inflammatory environment. Studies in PKC theta-deficient mice have demonstrated that while antiviral responses are PKC theta-independent, T cell responses associated with autoimmune diseases are PKC theta-dependent. Thus, potent and selective inhibition of PKC theta is expected to block autoimmune T cell responses without compromising antiviral immunity. Herein, we describe the development of potent and selective PKC theta inhibitors, which show exceptional potency in cells and in vivo. By use of a structure based rational design approach, a 1000-fold improvement in potency and 76-fold improvement in selectivity over closely related PKC isoforms such as PKC delta were obtained from the initial HTS hit, together with a big improvement in lipophilic efficiency (LiPE).

  DOI：

  10.1021/jm301465a