5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-hydroxy-2(1H)-quinolinone | 444663-59-6

• 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: 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-hydroxy-2(1H)-quinolinone
• 英文别名: 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-hydroxyquinolin-2-one
• CAS: 444663-59-6
• 化学式: C₂₁H₁₂Cl₃NO₂
• 分子量: 416.691
• InChiKey: STDZLCLOZACHQZ-UHFFFAOYSA-N

物化性质

• 沸点：
  626.1±55.0 °C(Predicted)
• 密度：
  1.483±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-hydroxy-2(1H)-quinolinone 在 platinum(IV) oxide 四(三苯基膦)钯 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium chloride 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-piperidin-4-ylquinolin-2(1H)-one
  参考文献：
  名称：

  p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

  摘要：

  We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-alpha release. The 4-aminopenta-methylpiperidine naphthyridinone 5, which was designed to block metabolism at major 'hot spots', combined excellent inhibitory potency with good oral bioavailability in the rat. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00990-3
• 作为产物：
  描述：

  5-bromo-1-(2,6-dichlorophenyl)-3,4-dihydro-7-methoxy-2(1H)-quinolinone 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 偶氮二异丁腈 、 三溴化硼 、 sodium carbonate 作用下， 以 四氯化碳 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-hydroxy-2(1H)-quinolinone
  参考文献：
  名称：

  p38 Inhibitors: piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones

  摘要：

  We have synthesized a series of C7-piperidine- and 4-aminopiperidine-substituted naphthyridinones, quinolinones, and dihydroquinazolinones that are highly potent inhibitors of both p38 MAP kinase activity and TNF-alpha release. The 4-aminopenta-methylpiperidine naphthyridinone 5, which was designed to block metabolism at major 'hot spots', combined excellent inhibitory potency with good oral bioavailability in the rat. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00990-3

文献信息

• (Halo-benzo carbonyl)heterocyclo fused phenyl p38 kinase inhibiting agents
  申请人：——

  公开号：US20030092712A1

  公开（公告）日：2003-05-15

  Compounds described by the chemical formula (I) or a pharmaceutically acceptable salt thereof: 1 are inhibitors of p38 useful in the treatment of inflammatory diseases such as arthritis.

  根据化学公式(I)或其药物可接受的盐描述的化合物： 1 是p38的抑制剂，可用于治疗类风湿性关节炎等炎症性疾病。
• [EN] (HALO-BENZO CARBONYL)HETEROCYCLO FUSED PHENYL P38 KINASE INHIBITING AGENTS<br/>[FR] AGENTS INHIBITEURS DE P38 KINASE (HALO-BENZO CARBONYL)HETEROCYCLO- FUSIONNES PHENYL
  申请人：MERCK & CO INC

  公开号：WO2002058695A1

  公开（公告）日：2002-08-01

  Compounds described by the chemical formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of p38 useful in the treatment of inflammatory diseases such as arthritis.

  化学式（I）或其药学上可接受的盐所描述的化合物是p38的抑制剂，可用于治疗炎症性疾病，如关节炎。
• Synthesis and biological activity of quinolinone and dihydroquinolinone p38 MAP kinase inhibitors
  作者：Meng-Hsin Chen、Patricia Fitzgerald、Suresh B. Singh、Edward A. O’Neill、Cheryl D. Schwartz、Chris M. Thompson、Stephen J. O’Keefe、Dennis M. Zaller、James B. Doherty

  DOI：10.1016/j.bmcl.2006.10.097

  日期：2008.3

  Synthesis and biological activities of some quinolinone and dihydroquinolinone p38 MAP kinase inhibitors are reported. Modi. cations to the dihydroquinolinone pharmacophore revealed that dihydroquinolinone may be replaced with a quinolinone pharmacophore and lead to enhanced p38 inhibitory activity. From a study of C-7 substitutions by amino acid side chains, a very potent series of compounds in the p38 enzyme assays was identified. Translation of the in vitro activity into reasonable whole blood activity can be improved in this series of compounds by judicious modi. cation of the physical properties at appropriate regions of the lead. (C) 2006 Elsevier Ltd. All rights reserved.
• p38 MAP kinase inhibitors: Metabolically stabilized piperidine-substituted quinolinones and naphthyridinones
  作者：Jianming Bao、Julianne A. Hunt、Shouwu Miao、Kathleen M. Rupprecht、John E. Stelmach、Luping Liu、Rowena D. Ruzek、Peter J. Sinclair、James V. Pivnichny、Cornelis E.C.A. Hop、Sanjeev Kumar、Dennis M. Zaller、Wesley L. Shoop、Edward A. O’Neill、Stephen J. O’Keefe、Chris M. Thompson、Rose M. Cubbon、Ruixiu Wang、Wen Xiao Zhang、James E. Thompson、James B. Doherty

  DOI：10.1016/j.bmcl.2005.09.065

  日期：2006.1

  Quinolinones and naphthyridinones with C7 N-t-butyl piperidine substituents were found to be potent p38 MAP kinase inhibitors. These compounds significantly suppress TNF-alpha release in both cellular and LPS-stimulated whole blood assays. They also displayed excellent PK profiles across three animal species. Quinolinone 4f at 10 mpk showed comparable oral efficacy to that of dexamethasone at 1 mpk in a murine collagen-induced arthritis model. (c) 2005 Elsevier Ltd. All rights reserved.
• EP1345603A4
  申请人：——

  公开号：EP1345603A4

  公开（公告）日：2004-09-08