N-(3,5-dichloropyridin-4-yl)-1-[3-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methylsulfonylphenyl)ethenyl]phenyl]-4-oxo-1,8-naphthyridine-3-carboxamide | 1088496-40-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N-(3,5-dichloropyridin-4-yl)-1-[3-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methylsulfonylphenyl)ethenyl]phenyl]-4-oxo-1,8-naphthyridine-3-carboxamide
• CAS: 1088496-40-5
• 化学式: C₃₂H₂₂Cl₂N₆O₅S
• 分子量: 673.536
• InChiKey: REEYYMDAALTGHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  46.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  149.94
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  4-氨基-3,5-二氯吡啶 、 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-(3,5-dichloropyridin-4-yl)-1-[3-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methylsulfonylphenyl)ethenyl]phenyl]-4-oxo-1,8-naphthyridine-3-carboxamide
  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

• 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.