3-(4-(tert-butyldimethylsilyl)-5-chloro-3-fluoro-6-((S)-3-((R)-3-methyl-2-(trimethylsilyloxy)butan-2-yl)piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine | 1321925-15-8

• 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-(4-(tert-butyldimethylsilyl)-5-chloro-3-fluoro-6-((S)-3-((R)-3-methyl-2-(trimethylsilyloxy)butan-2-yl)piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine
• 英文别名: tert-butyl-[3-chloro-5-fluoro-2-[(3S)-3-[(2R)-3-methyl-2-trimethylsilyloxybutan-2-yl]piperazin-1-yl]-6-(2H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-4-yl]-dimethylsilane
• CAS: 1321925-15-8
• 化学式: C₂₉H₄₆ClFN₆OSi₂
• 分子量: 605.346
• InChiKey: BOZPSOAHNNOJJC-AFJIDDCJSA-N

物化性质

• 沸点：
  629.6±55.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.57
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  79
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(4-(tert-butyldimethylsilyl)-5-chloro-3-fluoro-6-((S)-3-((R)-3-methyl-2-(trimethylsilyloxy)butan-2-yl)piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine 在 di-tert-butyl-[2-(2,4,6-triisopropylphenyl)]phosphane 、 四丁基氟化铵 、 potassium hydroxide 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 50.0h， 生成 5-fluoro-2-((S)-3-((R)-2-hydroxy-3-methylbutan-2-yl)piperazin-1-yl)-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)pyridin-3-ol bis(trifluoroacetate) salt
  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
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 正丁基锂 、 一水合肼 、 二异丙胺 、 calcium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 31.41h， 生成 3-(4-(tert-butyldimethylsilyl)-5-chloro-3-fluoro-6-((S)-3-((R)-3-methyl-2-(trimethylsilyloxy)butan-2-yl)piperazin-1-yl)pyridin-2-yl)-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

文献信息

• [EN] PYRAZOLOPYRIDINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PYRAZOLOPYRIDINE KINASE
  申请人：VERTEX PHARMA

  公开号：WO2011094273A1

  公开（公告）日：2011-08-04

  The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

  本发明涉及作为蛋白激酶抑制剂的化合物。该发明还提供了包括所述化合物的药学上可接受的组合物，以及使用这些组合物治疗各种疾病、症状或疾病的方法。该发明还提供了制备该发明化合物的方法。
• PYRAZOLOPYRIDINE KINASE INHIBITORS
  申请人：Boyall Dean

  公开号：US20120071494A1

  公开（公告）日：2012-03-22

  The present invention relates to compounds useful as inhibitors of protein kinase. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders. The invention also provides processes for preparing compounds of the inventions.

  本发明涉及用作蛋白激酶抑制剂的化合物。本发明还提供了包含该化合物的药学上可接受的组合物，并提供了使用该组合物治疗各种疾病、病况或障碍的方法。本发明还提供了制备本发明化合物的方法。
• Pyrazolopyridine kinase inhibitors
  申请人：Boyall Dean

  公开号：US09067932B2

  公开（公告）日：2015-06-30

  The present invention relates to compounds of pyrazolopyridine derivatives useful as inhibitors of protein kinase. In one embodiment the compounds of the present invention are represented by the following structural formula: or a pharmaceutically acceptable salt thereof.

  本发明涉及一种吡唑吡啶衍生物化合物，其可用作蛋白激酶的抑制剂。在一种实施例中，本发明的化合物由以下结构式表示：或其药学上可接受的盐。
• Design and Optimization of Selective Protein Kinase C θ (PKCθ) Inhibitors for the Treatment of Autoimmune Diseases
  作者：Juan-Miguel Jimenez、Dean Boyall、Guy Brenchley、Philip N. Collier、Christopher J. Davis、Damien Fraysse、Shazia B. Keily、Jaclyn Henderson、Andrew Miller、Francoise Pierard、Luca Settimo、Heather C. Twin、Claire M. Bolton、Adam P. Curnock、Peter Chiu、Adam J. Tanner、Stephen Young

  DOI：10.1021/jm301465a

  日期：2013.3.14

  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).