3-amino-5-[2-(methylamino)pyridin-4-yl]-1H-pyridin-2-one | 1276634-70-8

• 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-amino-5-[2-(methylamino)pyridin-4-yl]-1H-pyridin-2-one
• CAS: 1276634-70-8
• 化学式: C₁₁H₁₂N₄O
• 分子量: 216.242
• InChiKey: JXYBSYPUKLTGHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-哌嗪苯甲酸 、 3-amino-5-[2-(methylamino)pyridin-4-yl]-1H-pyridin-2-one 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 生成 3-(4-(piperidin-1-yl)benzoylamino)-5-(2-(methylamino)pyridin-4-yl)-(1H)-pyridin-2-one
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of 3-Aminopyrid-2-ones as Potent and Selective Interleukin-2 Inducible T-Cell Kinase (Itk) Inhibitors

  摘要：

  Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identified by structure-based design, starting from a fragment generated de novo, the 3-aminopyrid-2-one motif. Functionalization of the 3-amino group enabled rapid enhancement of the inhibitory activity against Itk, while introduction of a substituted heteroaromatic ring in position 5 of the pyridone fragment was key to achieving optimal selectivity over related kinases. A careful analysis of the hydration patterns in the kinase active. site was necessary to fully explain the observed selectivity profile. The best molecule prepared in this optimization campaign, 7v, inhibits Itk with a K-i of 7 nM and has a good selectivity profile across kinases.

  DOI：

  10.1021/jm101499u

文献信息

• ARYLPYRIDINONE ITK INHIBITORS FOR TREATING INFLAMMATION AND CANCER
  申请人：Confluence Life Sciences, Inc.

  公开号：US20150328227A1

  公开（公告）日：2015-11-19

  Disclosed herein are arylpyridinone compounds and compositions useful in the treatment of ITK mediated diseases, such as inflammation, having the structure of Formula (I): wherein Ar, R 2 , R 4 , R 5 , n and X are as defined in the detailed description. Methods of inhibition of ITK activity in a human or animal subject are also provided.

  本文披露了一种芳基吡啶酮化合物和组合物，其结构式（I）适用于治疗ITK介导的疾病，例如炎症，其中Ar，R2，R4，R5，n和X如详细描述中所定义的那样。还提供了在人或动物主体中抑制ITK活性的方法。