1-{3-[6-(1-Hydroxy-1-methyl-ethyl)-1-oxy-pyridin-3-ylethynyl]-phenyl}-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid cyclopropylamide | 500355-65-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-{3-[6-(1-Hydroxy-1-methyl-ethyl)-1-oxy-pyridin-3-ylethynyl]-phenyl}-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid cyclopropylamide
• 英文别名: N-cyclopropyl-1-[3-[2-[6-(2-hydroxypropan-2-yl)-1-oxidopyridin-1-ium-3-yl]ethynyl]phenyl]-4-oxo-1,8-naphthyridine-3-carboxamide
• CAS: 500355-65-7
• 化学式: C₂₈H₂₄N₄O₄
• 分子量: 480.523
• InChiKey: NADJKCIOGSRVDA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-Cyclopropyl-1-(3-bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide 、 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-{3-[6-(1-Hydroxy-1-methyl-ethyl)-1-oxy-pyridin-3-ylethynyl]-phenyl}-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid cyclopropylamide
  参考文献：
  名称：

  Optimization and structure–activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 inhibitor

  摘要：

  A SAR study of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS-induced production of TNF-alpha in human whole blood and minimizing affinity for the hERG potassium channel. From these studies, compounds 18 and 20 (MK-0873) were identified as optimized PDE4 inhibitors with good overall in vitro and in vivo profiles and selected as development candidates. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.09.009

文献信息

• Alkyne-aryl phosphodiesterase-4 inhibitors
  申请人：——

  公开号：US20030114478A1

  公开（公告）日：2003-06-19

  Compounds represented by Formula (I): 1 or a pharmaceutically acceptable salt thereof, are phosphodiesterase 4 inhibitors useful in the treatment of asthma and inflammation.

  由公式（I）表示的化合物1或其药学上可接受的盐，是磷酸二酯酶4抑制剂，可用于哮喘和炎症的治疗。
• Use of phosphodiesterase-4 inhibitors as enhancers of cognition
  申请人：Dube Daniel

  公开号：US20060040981A1

  公开（公告）日：2006-02-23

  The present invention is directed to a method of enhancing cognition in a healthy subject comprising administering a safe cognition enhancing amount of a phosphodiesterase-4 inhibitor. In particular, this invention is directed to a method of enhancing memory, learning, retention, recall, awareness and judgement in health subjects comprising administering a safe and effective amount of a phosphodiesterase-4 inhibitor.

  本发明涉及一种增强健康受试者认知能力的方法，包括给予安全的磷酸二酯酶-4抑制剂增强认知能力的剂量。特别地，本发明涉及一种增强健康受试者记忆、学习、保留、回忆、意识和判断力的方法，包括给予安全有效的磷酸二酯酶-4抑制剂的剂量。
• Use of pde4 inhibitors as adjunct therapy for psychiatric disorders
  申请人：Scolnick M. Edward

  公开号：US20060069115A1

  公开（公告）日：2006-03-30

  The use of a PDE4 inhibitor in conjunction with psychotherapy provides enhanced therapeutic results in the treatment of psychiatric disorders including, for example, specific phobias, panic disorders, anxiety disorders including posttraumatic stress disorders, and obsessive-compulsive disorder.

  在治疗精神障碍，例如特定恐惧症、惊恐障碍、包括创伤后应激障碍和强迫症的焦虑障碍中，与心理治疗同时使用PDE4抑制剂可以提供增强的治疗效果。
• Optimization and structure–activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: Identification of MK-0873, a potent and effective PDE4 inhibitor
  作者：Daniel Guay、Louise Boulet、Richard W. Friesen、Mario Girard、Pierre Hamel、Zheng Huang、France Laliberté、Sébastien Laliberté、Joseph A. Mancini、Eric Muise、Doug Pon、Angela Styhler

  DOI：10.1016/j.bmcl.2008.09.009

  日期：2008.10

  A SAR study of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS-induced production of TNF-alpha in human whole blood and minimizing affinity for the hERG potassium channel. From these studies, compounds 18 and 20 (MK-0873) were identified as optimized PDE4 inhibitors with good overall in vitro and in vivo profiles and selected as development candidates. (c) 2008 Elsevier Ltd. All rights reserved.