(3,6-difluoropyridin-2-yl)(2-fluoropyridin-3-yl)methanone | 1206625-38-8

• 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: (3,6-difluoropyridin-2-yl)(2-fluoropyridin-3-yl)methanone
• 英文别名: (3,6-difluoro-2-pyridyl)-(2-fluoro-3-pyridyl)methanone；(3,6-Difluoropyridin-2-yl)-(2-fluoropyridin-3-yl)methanone
• CAS: 1206625-38-8
• 化学式: C₁₁H₅F₃N₂O
• 分子量: 238.169
• InChiKey: NGEMJXGREAEEIU-UHFFFAOYSA-N

物化性质

• 沸点：
  390.6±42.0 °C(Predicted)
• 密度：
  1.429±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3,6-difluoropyridin-2-yl)(2-fluoropyridin-3-yl)methanone 在 一水合肼 作用下， 以 四氢呋喃 为溶剂， 以55.5%的产率得到3-(3,6-difluoropyridin-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
• 作为产物：
  描述：

  2-氟-N-甲氧基-N-甲基烟酰胺 、 2,5-二氟吡啶 在 三乙烯二胺 、 正丁基锂 、 水 、 氯化铵 作用下， 以 四氢呋喃 、 甲基叔丁基醚 为溶剂， 反应 1.0h， 以54%的产率得到(3,6-difluoropyridin-2-yl)(2-fluoropyridin-3-yl)methanone
  参考文献：
  名称：

  [EN] TRI-CYCLIC PYRAZOLOPYRIDINE KINASE INHIBITORS
  [FR] INHIBITEURS DE LA PYRAZOLOPYRIDINE KINASE TRICYCLIQUE

  摘要：

  公开号：

  WO2010011772A3

文献信息

• TRI-CYCLIC PYRAZOLOPYRIDINE KINASE INHIBITORS
  申请人：Jimenez Juan-Miguel

  公开号：US20120136000A1

  公开（公告）日：2012-05-31

  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。本发明还提供了包括所述化合物的药学上可接受的组合物以及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该发明化合物的方法。
• [EN] TRI-CYCLIC PYRAZOLOPYRIDINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PYRAZOLOPYRIDINE KINASE TRICYCLIQUE
  申请人：VERTEX PHARMA

  公开号：WO2010011772A3

  公开（公告）日：2010-04-29
• US8569337B2
  申请人：——

  公开号：US8569337B2

  公开（公告）日：2013-10-29
• US9193722B2
  申请人：——

  公开号：US9193722B2

  公开（公告）日：2015-11-24
• 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).