1-[3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]cyclopentane-1-carbonitrile | 1160499-06-8

• 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: 1-[3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]cyclopentane-1-carbonitrile
• CAS: 1160499-06-8
• 化学式: C₁₈H₁₆N₄
• 分子量: 288.352
• InChiKey: JHCYXYREDIUVGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-[3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]cyclopentane-1-carbonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以11%的产率得到(1-(3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)cyclopentyl)methanamine
  参考文献：
  名称：

  Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis

  摘要：

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.9b00134
• 作为产物：
  描述：

  3-溴氰苄 在 三乙基硅烷 、 二(三叔丁基膦)钯 、 sodium hydride 、 sodium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 3.83h， 生成 1-[3-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]cyclopentane-1-carbonitrile
  参考文献：
  名称：

  Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis

  摘要：

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.9b00134

文献信息

• KINASE INHIBITORS
  申请人：Jimenez Juan-Miguel

  公开号：US20090291937A1

  公开（公告）日：2009-11-26

  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上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本发明化合物的方法。
• US8173635B2
  申请人：——

  公开号：US8173635B2

  公开（公告）日：2012-05-08
• US8367697B2
  申请人：——

  公开号：US8367697B2

  公开（公告）日：2013-02-05
• Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis
  作者：Philip N. Collier、Heather C. Twin、Ronald M. A. Knegtel、Dean Boyall、Guy Brenchley、Christopher J. Davis、Shazia Keily、Chau Mak、Andrew Miller、Françoise Pierard、Luca Settimo、Clare M. Bolton、Peter Chiu、Adam Curnock、Elisabeth Doyle、Adam J. Tanner、Juan-Miguel Jimenez

  DOI：10.1021/acsmedchemlett.9b00134

  日期：2019.8.8

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.