2-methyl-3-(4-nitrophenoxy)pyridine | 1362703-08-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-methyl-3-(4-nitrophenoxy)pyridine
• 英文别名: 3-(4-nitrophenoxy)-2-methylpyridine
• CAS: 1362703-08-9
• 化学式: C₁₂H₁₀N₂O₃
• 分子量: 230.223
• InChiKey: FIZCWDFHYGZNKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-3-(4-nitrophenoxy)pyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 potassium acetate 、 碳酸氢钠 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.34h， 生成 1-butyl-4-[4-(2-methylpyridin-3-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile
  参考文献：
  名称：

  Discovery of 1,4-Disubstituted 3-Cyano-2-pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

  摘要：

  The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak in vitro activity of the hit 13 was quickly improved, although compounds still had suboptimal druglike properties. Subsequent modulation of the physicochemical properties resulted in compounds having a more balanced profile, combining good potency and in vivo pharmacokinetic properties. Final refinement by addressing cardiovascular safety liabilities led to the discovery of compound 48. Besides good potency, selectivity, and ADME properties, compound 48 displayed robust in vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with mGlu2 receptor activation, in accordance with previous work from our laboratories.

  DOI：

  10.1021/jm2016864
• 作为产物：
  描述：

  3-羟基-2-甲基吡啶 、 对氟硝基苯 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71.1%的产率得到2-methyl-3-(4-nitrophenoxy)pyridine
  参考文献：
  名称：

  [EN] PYRIDAZINONES AND METHODS OF USE THEREOF
  [FR] PYRIDAZINONES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2019055966A3

文献信息

• [EN] PYRIDAZINONES AND METHODS OF USE THEREOF<br/>[FR] PYRIDAZINONES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GOLDFINCH BIO INC

  公开号：WO2019055966A3

  公开（公告）日：2019-04-18
• PYRIDAZINONES AND METHODS OF USE THEREOF
  申请人：Goldfinch Bio, Inc.

  公开号：EP3684364A2

  公开（公告）日：2020-07-29
• Discovery of 1,4-Disubstituted 3-Cyano-2-pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor
  作者：Jose María Cid、Guillaume Duvey、Gary Tresadern、Vanthea Nhem、Rocco Furnari、Philippe Cluzeau、Juan Antonio Vega、Ana Isabel de Lucas、Encarnación Matesanz、José Manuel Alonso、María Lourdes Linares、José Ignacio Andrés、Sonia M. Poli、Robert Lutjens、Hassan Himogai、Jean-Philippe Rocher、Gregor J. Macdonald、Daniel Oehlrich、Hilde Lavreysen、Abdelah Ahnaou、Wilhelmus Drinkenburg、Claire Mackie、Andrés A. Trabanco

  DOI：10.1021/jm2016864

  日期：2012.3.8

  The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak in vitro activity of the hit 13 was quickly improved, although compounds still had suboptimal druglike properties. Subsequent modulation of the physicochemical properties resulted in compounds having a more balanced profile, combining good potency and in vivo pharmacokinetic properties. Final refinement by addressing cardiovascular safety liabilities led to the discovery of compound 48. Besides good potency, selectivity, and ADME properties, compound 48 displayed robust in vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with mGlu2 receptor activation, in accordance with previous work from our laboratories.