4-chloro-6-(isopropylthio)quinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-chloro-6-(isopropylthio)quinoline
• 英文别名: 4-Chloro-6-(isopropylthio)quinoline；4-chloro-6-propan-2-ylsulfanylquinoline
• 化学式: C₁₂H₁₂ClNS
• 分子量: 237.753
• InChiKey: FMGHDXSJFAHCEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-6-(isopropylthio)quinoline 在 oxone 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以80%的产率得到4-chloro-6-[(1-methylethyl)sulfonyl]quinoline
  参考文献：
  名称：

  The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase

  摘要：

  RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.6b00211
• 作为产物：
  描述：

  5-{[(4-iodophenyl)amino]methylidene}-2,2-dimethyl-1,3-dioxane-4,6-dione 在 四(三苯基膦)钯 、 potassium tert-butylate 、 三氯氧磷 作用下， 以 二苯醚 、 甲苯 为溶剂， 反应 2.5h， 生成 4-chloro-6-(isopropylthio)quinoline
  参考文献：
  名称：

  The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase

  摘要：

  RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.6b00211

文献信息

• AMINO-QUINOLINES AS KINASE INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP2566477B1

  公开（公告）日：2015-09-02
• The Identification and Pharmacological Characterization of 6-(<i>tert</i>-Butylsulfonyl)-<i>N</i>-(5-fluoro-1<i>H</i>-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase
  作者：Pamela A. Haile、Bartholomew J. Votta、Robert W. Marquis、Michael J. Bury、John F. Mehlmann、Robert Singhaus、Adam K. Charnley、Ami S. Lakdawala、Máire A. Convery、David B. Lipshutz、Biva M. Desai、Barbara Swift、Carol A. Capriotti、Scott B. Berger、Mukesh K. Mahajan、Michael A. Reilly、Elizabeth J. Rivera、Helen H. Sun、Rakesh Nagilla、Allison M. Beal、Joshua N. Finger、Michael N. Cook、Bryan W. King、Michael T. Ouellette、Rachel D. Totoritis、Maria Pierdomenico、Anna Negroni、Laura Stronati、Salvatore Cucchiara、Bartłomiej Ziółkowski、Anna Vossenkämper、Thomas T. MacDonald、Peter J. Gough、John Bertin、Linda N. Casillas

  DOI：10.1021/acs.jmedchem.6b00211

  日期：2016.5.26

  RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.