4-(2-methylpyridin-3-yloxy)-3-chlorophenylamine | 1362703-20-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(2-methylpyridin-3-yloxy)-3-chlorophenylamine
• 英文别名: 3-chloro-4-(2-methylpyridin-3-yl)oxyaniline
• CAS: 1362703-20-5
• 化学式: C₁₂H₁₁ClN₂O
• 分子量: 234.685
• InChiKey: VZGOLOWHXIFQKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 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：
  48.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-methylpyridin-3-yloxy)-3-chlorophenylamine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 氢溴酸 、 potassium acetate 、 碳酸氢钠 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 为溶剂， 反应 7.17h， 生成 1-cyclopropylmethyl-4-[3-chloro-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-氯-4-氟硝基苯 在 caesium carbonate 、 tin(ll) chloride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 4-(2-methylpyridin-3-yloxy)-3-chlorophenylamine
  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

文献信息

• Substituted bicyclic derivatives for the treatment of abnormal cell growth
  申请人：——

  公开号：US20020169165A1

  公开（公告）日：2002-11-14

  The invention relates to compounds of the formula 1 1 and to pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein R 1 , R 3 , R 4 , R 5 , R 11 , m and p are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of formula 1. The invention also relates to methods of preparing the compounds of formula 1.

  该发明涉及公式11的化合物，以及其药学上可接受的盐、前药和溶剂化物，其中R1、R3、R4、R5、R11、m和p如本文所定义。该发明还涉及通过给予公式1的化合物治疗哺乳动物的异常细胞增长的方法，并且涉及用含有公式1的化合物的制药组合物治疗这种疾病的方法。该发明还涉及制备公式1的化合物的方法。
• SUBSTITUTED BICYCLIC DERIVATIVES FOR THE TREATMENT OF ABNORMAL CELL GROWTH
  申请人：Pfizer Products Inc.

  公开号：EP1292591B1

  公开（公告）日：2005-02-02
• US6890924B2
  申请人：——

  公开号：US6890924B2

  公开（公告）日：2005-05-10
• US7332493B2
  申请人：——

  公开号：US7332493B2

  公开（公告）日：2008-02-19
• 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.