3-(6-chloropyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine | 1422207-24-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 3-(6-chloropyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine
• 英文别名: 3-(6-chloropyridin-2-yl)-2H-pyrazolo[3,4-b]pyridine
• CAS: 1422207-24-6
• 化学式: C₁₁H₇ClN₄
• 分子量: 230.656
• InChiKey: SEIBYUKVPQRTDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 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：
  54.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(6-chloropyridin-2-yl)-1H-pyrazolo[3,4-b]pyridine 、 (R)-(-)-2-甲基哌嗪 在 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 以18%的产率得到3-[6-[(3R)-3-methylpiperazin-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
• 作为产物：
  描述：

  2-氟-N-甲氧基-N-甲基烟酰胺 在 正丁基锂 、 N,N-二甲基乙醇胺 、 肼 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 2.83h， 生成 3-(6-chloropyridin-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

• 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).