N-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]nicotinamide

• 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: N-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]nicotinamide
• 英文别名: N-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide
• 化学式: C₂₁H₁₈N₄O₃
• 分子量: 374.399
• InChiKey: ACBZBWFKUGVGRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  89.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-溴-3-((三甲基甲硅烷基)乙炔)吡啶-2-胺 在 吡啶 、 potassium tert-butylate 、 氢气 、 硝酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N-甲基吡咯烷酮 、 二氯甲烷 、 水 为溶剂， 反应 5.01h， 生成 N-[5-(3,4-dimethoxyphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]nicotinamide
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3-b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity

  摘要：

  There are currently no approved drugs for the treatment of emerging viral infections, such as dengue and Ebola. Adaptor-associated kinase 1 (AAK1) is a cellular serine-threonine protein kinase that functions as a key regulator of the clathrin-associated host adaptor proteins and regulates the intracellular trafficking of multiple unrelated RNA viruses. Moreover, AAK1 is overexpressed specifically in dengue virus-infected but not bystander cells. Because AAK1 is a promising antiviral drug target, we have embarked on an optimization campaign of a previously identified 7-azaindole analogue, yielding novel pyrrolo[2,3-b]pyridines with high AAK1 affinity. The optimized compounds demonstrate improved activity against dengue virus both in vitro and in human primary dendritic cells and the unrelated Ebola virus. These findings demonstrate that targeting cellular AAK1 may represent a promising broad-spectrum antiviral strategy.

  DOI：

  10.1021/acs.jmedchem.9b00136

文献信息

• [EN] CHK1 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA KINASE CHK1
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2003028724A1

  公开（公告）日：2003-04-10

  Novel compounds useful in the inhibition of damage response kinases are provided.
• Synthesis and Structure–Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3-<i>b</i>]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity
  作者：Sven Verdonck、Szu-Yuan Pu、Fiona J. Sorrell、Jon M. Elkins、Mathy Froeyen、Ling-Jie Gao、Laura I. Prugar、Danielle E. Dorosky、Jennifer M. Brannan、Rina Barouch-Bentov、Stefan Knapp、John M. Dye、Piet Herdewijn、Shirit Einav、Steven De Jonghe

  DOI：10.1021/acs.jmedchem.9b00136

  日期：2019.6.27

  There are currently no approved drugs for the treatment of emerging viral infections, such as dengue and Ebola. Adaptor-associated kinase 1 (AAK1) is a cellular serine-threonine protein kinase that functions as a key regulator of the clathrin-associated host adaptor proteins and regulates the intracellular trafficking of multiple unrelated RNA viruses. Moreover, AAK1 is overexpressed specifically in dengue virus-infected but not bystander cells. Because AAK1 is a promising antiviral drug target, we have embarked on an optimization campaign of a previously identified 7-azaindole analogue, yielding novel pyrrolo[2,3-b]pyridines with high AAK1 affinity. The optimized compounds demonstrate improved activity against dengue virus both in vitro and in human primary dendritic cells and the unrelated Ebola virus. These findings demonstrate that targeting cellular AAK1 may represent a promising broad-spectrum antiviral strategy.