(E)-5-{[1-(2-chloro-3-fluoro-4-methoxyphenyl)methylidene]-amino}-7-fluoro-1H-quinolin-2-one | 2493327-79-8

• 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: (E)-5-{[1-(2-chloro-3-fluoro-4-methoxyphenyl)methylidene]-amino}-7-fluoro-1H-quinolin-2-one
• CAS: 2493327-79-8
• 化学式: C₁₇H₁₁ClF₂N₂O₂
• 分子量: 348.736
• InChiKey: NSHOAWRJSKLFEE-ODCIPOBUSA-N

物化性质

• 沸点：
  590.0±50.0 °C (Predicted,Press: 760 Torr)
• 密度：
  1.40±0.1 g/cm³ (Predicted,Temp: 20 °C; Press: 760 Torr)
• pKa：
  10.30±0.70 (Predicted,Most Acidic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  54.45
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (E)-5-{[1-(2-chloro-3-fluoro-4-methoxyphenyl)methylidene]-amino}-7-fluoro-1H-quinolin-2-one 在 正丁基锂 、 高氯酸 、 sodium hydride 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 71.17h， 生成 5-{(1S,2S)-[1-(2-chloro-3-fluoro-4-methoxyphenyl)-3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]amino}-7-fluoro-1H-quinolin-2-one
  参考文献：
  名称：

  Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate

  摘要：

  We report on the discovery of the new clinical candidate BAY 1003803 as glucocorticoid receptor agonist for the topical treatment of psoriasis or severe atopic dermatitis. In the course of optimizing the amino alcohol series as a highly potent new non-steroidal lead structure, considerations were made as to how physicochemical properties and safety concerns relate to structural motifs. BAY 1003803 demonstrates strong anti-inflammatory activity in vitro paired with a pharmacokinetic profile suitable for topical application.

  DOI：

  10.1016/j.bmcl.2020.127298
• 作为产物：
  描述：

  5-amino-7-fluoro-1H-quinolin-2-one 、 2-氯-3-氟-4-甲氧基苯甲醛 在 titanium(IV) tetrabutoxide 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 20.0h， 以92%的产率得到(E)-5-{[1-(2-chloro-3-fluoro-4-methoxyphenyl)methylidene]-amino}-7-fluoro-1H-quinolin-2-one
  参考文献：
  名称：

  Discovery of the potent non-steroidal glucocorticoid receptor modulator BAY 1003803 as clinical candidate

  摘要：

  We report on the discovery of the new clinical candidate BAY 1003803 as glucocorticoid receptor agonist for the topical treatment of psoriasis or severe atopic dermatitis. In the course of optimizing the amino alcohol series as a highly potent new non-steroidal lead structure, considerations were made as to how physicochemical properties and safety concerns relate to structural motifs. BAY 1003803 demonstrates strong anti-inflammatory activity in vitro paired with a pharmacokinetic profile suitable for topical application.

  DOI：

  10.1016/j.bmcl.2020.127298

文献信息

• 5-[(3,3,3-Trifluoro-2-hydroxy-1-arylpropyl)amino]-1H-quinolin-2-ones, A Process for Their Production and Their Use as Anti-inflammatory Agents
  申请人：Berger Markus

  公开号：US20090137564A1

  公开（公告）日：2009-05-28

  The present invention relates to compounds of formula I, processes for their production and their use as anti-inflammatory agents.

  本发明涉及公式I的化合物，其生产过程以及作为抗炎药物的用途。
• 5-[(3,3,3-Trifluoro-2-hydroxy-1-arylpropyl)amino-1-arylquinolin-2-ones, a process for their production and their use as anti-inflammatory agents
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2149558A1

  公开（公告）日：2010-02-03

  The present invention relates to compounds of formula I, processes and intermediates for their production and their use as antiinflammatory agents.

  本发明涉及公式I的化合物，其生产过程和中间体，以及作为抗炎药物的用途。
• 5-[(3,3,3-Trifluoro-2-hydroxy-1-arylpropyl)amino]-1-arylquinolin-2-ones, a Process for their Production and their Use as Anti-inflammatory Agents
  申请人：Berger Markus

  公开号：US20100016338A1

  公开（公告）日：2010-01-21

  The present invention relates to compounds of formula I, processes and intermediates for their production and their use as anti-inflammatory agents.

  本发明涉及式I的化合物，其生产过程和中间体，以及作为抗炎药物的用途。
• 5-[(3,3,3-TRIFLUORO-2-HYDROXY-1-ARYLPROPYL)AMINO]-1H-QUINOLIN-2-ONES, A PROCESS FOR THEIR PRODUCTION AND THEIR USE AS ANTI-INFLAMMATORY AGENTS
  申请人：BERGER Markus

  公开号：US20130005766A1

  公开（公告）日：2013-01-03

  The present invention relates to compounds of formula I, processes for their production and their use as anti-inflammatory agents.

  本发明涉及式I的化合物，其制备过程以及其作为抗炎剂的用途。
• 5-[(3,3,3-Trifluoro-2-hydroxy-1-arylpropyl)amino]-1H-quinolin-2-ones, a process for their production and their use as anti-inflammatory agents
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP2062880A1

  公开（公告）日：2009-05-27

  The present invention relates to compounds of formula I, processes for their production and their use as anti-inflammatory agents.

  本发明涉及式 I 的化合物、 的生产工艺及其作为抗炎剂的用途。