tert-butyl-[(2,6-dichloro-5-fluoro-3-pyridyl)methoxy]dimethylsilane | 1422207-31-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: tert-butyl-[(2,6-dichloro-5-fluoro-3-pyridyl)methoxy]dimethylsilane
• CAS: 1422207-31-5
• 化学式: C₁₂H₁₈Cl₂FNOSi
• 分子量: 310.271
• InChiKey: RZVUAORUAJRMJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.05
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  22.12
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)-1-三苯甲游基-吡唑并[5,4-b]吡啶 、 tert-butyl-[(2,6-dichloro-5-fluoro-3-pyridyl)methoxy]dimethylsilane 在 copper(l) iodide 、 四(三苯基膦)钯 、 cesium fluoride 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.0h， 以39%的产率得到3-(5-(((tert-butyl-dimethylsilyl)oxy)methyl)-6-chloro-3-fluoropyridin-2-yl)-1-trityl-1H-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