4-(4-bromo-2-fluorophenoxy)-2,6-dimethylpyridine | 1056462-15-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(4-bromo-2-fluorophenoxy)-2,6-dimethylpyridine
• 英文别名: 4-(4-Bromo-2-fluoro-phenoxy)-2,6-dimethyl-pyridine
• CAS: 1056462-15-7
• 化学式: C₁₃H₁₁BrFNO
• 分子量: 296.139
• InChiKey: VUXVWXFRPPTAMC-UHFFFAOYSA-N

物化性质

• 沸点：
  310.6±42.0 °C(Predicted)
• 密度：
  1.436±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2-fluorophenoxy)-2,6-dimethylpyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 、 potassium acetate 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.17h， 生成 1-butyl-4-[3-fluoro-4-(2,6-dimethylpyridin-4-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：

  4-氯-2,6-二甲基吡啶 、 4-溴-2-氟苯酚 在 potassium carbonate 作用下， 以66%的产率得到4-(4-bromo-2-fluorophenoxy)-2,6-dimethylpyridine
  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

• [EN] 1,3-DISUBSTITUTED 4-(ARYL-X-PHENYL)-1H-PYRIDIN-2-ONES<br/>[FR] 4-(ARYL-X-PHÉNYL)-1H-PYRIDINE-2-ONES 1,3-DISUBSTITUÉES
  申请人：ORTHO MCNEIL JANSSEN PHARM

  公开号：WO2009033702A1

  公开（公告）日：2009-03-19

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I), wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors - subtype 2 ('mGluR2') which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新化合物，特别是根据式（I）的新吡啶酮衍生物，其中所有基团如申请和索赔中所定义。根据本发明的化合物是代谢型受体-亚型2（'mGluR2'）的阳性别构调节剂，对与谷氨酸功能障碍相关的神经系统和精神障碍以及涉及代谢型受体亚型mGluR2的疾病的治疗或预防是有用的。具体来说，这些疾病是从焦虑、精神分裂症、偏头痛、抑郁症和癫痫等疾病组中选择的中枢神经系统疾病。该发明还涉及制备这种化合物和组合物的药物组合物和方法，以及利用这种化合物预防和治疗涉及mGluR2的这些疾病。
• 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE MGLUR2-RECEPTOR MODULATORS
  申请人：Cid-Núñez José Maria

  公开号：US20100099715A1

  公开（公告）日：2010-04-22

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic glutamate receptors subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and such compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是公式（I）中的新型吡啶酮衍生物，包括其任何立体化异构体形式，或其药学上可接受的盐或溶剂，其中所有基团在申请和权利要求中都有定义。本发明所述化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正向变构调节剂，可用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及涉及代谢型受体亚型mGluR2的疾病。特别是，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病。本发明还涉及制备这种化合物和这种组合物的制药组合物和过程，以及使用这种化合物预防和治疗涉及mGluR2的这种疾病。
• 1,3-DISUBSTITUTED 4-(ARYL-X-PHENYL)-1H-PYRIDIN-2-ONES
  申请人：DUVEY Guillaume Albert Jacques

  公开号：US20120309793A1

  公开（公告）日：2012-12-06

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors—subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新颖化合物，特别是公式（I）中定义的新型吡啶酮衍生物，其中所有基团均如申请和权利要求中所定义。本发明的化合物是代谢型受体-亚型2（“mGluR2”）的正变构调节剂，可用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型受体mGluR2亚型的疾病。特别是，这些疾病是从焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病组中选择的。本发明还涉及制备这样的化合物和组合物的制药组合物和过程，以及使用这些化合物预防和治疗涉及mGluR2的这些疾病。
• 1,3-disubstituted 4-(aryl-X-phenyl)-1H-pyridin-2-ones
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：US08252937B2

  公开（公告）日：2012-08-28

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) wherein all radicals are as defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors—subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新型化合物，特别是公式（I）中定义的新型吡啶酮衍生物，其中所有基团均如本申请和权利要求所定义。本发明的化合物是代谢型受体亚型2（“mGluR2”）的正向变构调节剂，可用于治疗或预防与谷氨酸功能障碍有关的神经和精神障碍以及涉及代谢型受体亚型mGluR2的疾病。特别是，这些疾病是选自焦虑、精神分裂症、偏头痛、抑郁症和癫痫等中枢神经系统疾病的一组。本发明还涉及制备这些化合物和组合物的制药组合物和过程，以及将这些化合物用于预防和治疗涉及mGluR2的这些疾病的用途。
• 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE DERIVATIVES AND THEIR USE AS POSITIVE MGLUR2-RECEPTOR
  申请人：Cid-Nunez Jose Maria

  公开号：US20130150412A1

  公开（公告）日：2013-06-13

  The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I) including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic glutamate receptors subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and such compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

  本发明涉及新颖化合物，特别是根据式（I）的新颖吡啶酮衍生物，包括其任何立体化异构体形式，或其药学上可接受的盐或溶剂化物，其中所有基团在申请和权利要求中都有定义。本发明所述化合物是代谢型谷氨酸受体亚型2（“mGluR2”）的正向变构调节剂，对于与谷氨酸功能障碍和mGluR2代谢型受体有关的神经和精神障碍以及疾病的治疗或预防是有用的。特别是，这些疾病是选择自焦虑、精神分裂症、偏头痛、抑郁症和癫痫的中枢神经系统疾病。本发明还涉及制备这些化合物和这些组合物的制药组合物和制备过程，以及使用这些化合物预防和治疗与mGluR2有关的这些疾病。