3-[4-(1-hydroxymethyl-cyclopropylcarbamoyl)-benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester | 1392482-80-2

• 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: 3-[4-(1-hydroxymethyl-cyclopropylcarbamoyl)-benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester
• 英文别名: Methyl 3-[[4-[[1-(hydroxymethyl)cyclopropyl]carbamoyl]phenyl]methyl]-4-oxo-1-phenyl-1,8-naphthyridine-2-carboxylate；methyl 3-[[4-[[1-(hydroxymethyl)cyclopropyl]carbamoyl]phenyl]methyl]-4-oxo-1-phenyl-1,8-naphthyridine-2-carboxylate
• CAS: 1392482-80-2
• 化学式: C₂₈H₂₅N₃O₅
• 分子量: 483.524
• InChiKey: CIOSNPUPZXNFLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(2-(phenylamino)pyridin-3-yl)ethanone 在 10% Pd/C 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 sodium methylate 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 82.0h， 生成 3-[4-(1-hydroxymethyl-cyclopropylcarbamoyl)-benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor

  摘要：

  3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-alpha challenge models.

  DOI：

  10.1021/ml300175c

文献信息

• Identification of an Adamantyl Azaquinolone JNK Selective Inhibitor
  作者：Nancy-Ellen Haynes、Nathan R. Scott、Li C. Chen、Cheryl A. Janson、Jia Kui Li、Christine M. Lukacs、Aruna Railkar、Effie Tozzo、Toni Whittard、Nicholas F. Brown、Adrian Wai-Hing Cheung

  DOI：10.1021/ml300175c

  日期：2012.9.13

  3-[4-((1S,2S,3R,5S,7S)-5-Hydroxyadamantan-2-ylcarbamoyl)benzyl]-4-oxo-1-phenyl-1,4-dihydro-[1,8]naphthyridine-2-carboxylic acid methyl ester (4) was identified as a novel, druglike and selective quinolone pan JNK inhibitor. In this communication, some of the structure activity relationship of the azaquinolone analogues leading to 4 is discussed. The focus is on how changes at the amide functionality affected the biochemical potency, cellular potency, metabolic properties, and solubility of this class of JNK inhibitors. Optimization of these properties led to the identification of the adamantyl analogue, 4. 4 achieved proof of mechanism in both rat and mouse TNF-alpha challenge models.