2-(2-(2-chlorophenyl)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one

• 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: 2-(2-(2-chlorophenyl)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
• 英文别名: Pyrrolopyridine, 20；2-[2-(2-chlorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one
• 化学式: C₁₈H₁₄ClN₃O
• 分子量: 323.782
• InChiKey: ZNCHVQUSJFJKLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(2-(2-chlorophenyl)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one 在 4-二甲氨基吡啶 、 potassium [¹⁸F]fluoride 、 [Cu(OTf)(IPr)] 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以5%的产率得到
  参考文献：
  名称：

  NHC-铜介导的芳基卤化物的配体定向放射性氟化

  摘要：

  [18F] 标记的芳基氟化物被广泛用作正电子发射断层扫描 (PET) 成像的放射性示踪剂。芳基卤化物 (ArX) 是这些放射性示踪剂特别有吸引力的前体，因为它们易于获得、价格低廉且稳定。然而，迄今为止，从芳基卤化物直接制备 [18F]-芳基氟化物仍然仅限于高度活化的 ArX 底物和 K18F 之间的 SNAr 反应。本报告描述了一种芳基卤化物放射性氟化反应，其中 C(sp2)-18F 键是通过铜介导的途径形成的。铜 N-杂环卡宾配合物用作这种转化的介体，使用在邻位具有导向基团的芳基卤化物底物。该反应适用于电子不同的芳基卤化物衍生物的放射性氟化，

  DOI：

  10.1021/jacs.0c02637
• 作为产物：
  描述：

  2-氯-4-乙酰吡啶 在 四(三苯基膦)钯 ammonium acetate 、 氢溴酸 、 溴 、 caesium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-(2-(2-chlorophenyl)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one
  参考文献：
  名称：

  Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2)

  摘要：

  A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNF alpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.

  DOI：

  10.1021/jm0611004

文献信息

• NHC-Copper Mediated Ligand-Directed Radiofluorination of Aryl Halides
  作者：Liam S. Sharninghausen、Allen F. Brooks、Wade P. Winton、Katarina J. Makaravage、Peter J. H. Scott、Melanie S. Sanford

  DOI：10.1021/jacs.0c02637

  日期：2020.4.22

  which the C(sp2)-18F bond is formed via a copper-mediated pathway. Copper N-heterocyclic carbene complexes serve as mediators for this transformation, using aryl halide substrates with directing groups at the ortho position. This reaction is applied to the radiofluorination of electronically diverse aryl halide derivatives, including the bioactive molecules vismodegib and PH-089.

  [18F] 标记的芳基氟化物被广泛用作正电子发射断层扫描 (PET) 成像的放射性示踪剂。芳基卤化物 (ArX) 是这些放射性示踪剂特别有吸引力的前体，因为它们易于获得、价格低廉且稳定。然而，迄今为止，从芳基卤化物直接制备 [18F]-芳基氟化物仍然仅限于高度活化的 ArX 底物和 K18F 之间的 SNAr 反应。本报告描述了一种芳基卤化物放射性氟化反应，其中 C(sp2)-18F 键是通过铜介导的途径形成的。铜 N-杂环卡宾配合物用作这种转化的介体，使用在邻位具有导向基团的芳基卤化物底物。该反应适用于电子不同的芳基卤化物衍生物的放射性氟化，
• Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2)
  作者：David R. Anderson、Marvin J. Meyers、William F. Vernier、Matthew W. Mahoney、Ravi G. Kurumbail、Nicole Caspers、Gennadiy I. Poda、John F. Schindler、David B. Reitz、Robert J. Mourey

  DOI：10.1021/jm0611004

  日期：2007.5.1

  A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNF alpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.