4-[3-fluoro-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2-methylpyridine | 1128149-88-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[3-fluoro-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2-methylpyridine
• 英文别名: 4-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]-2-methylpyridine
• CAS: 1128149-88-1
• 化学式: C₁₈H₂₁BFNO₃
• 分子量: 329.179
• InChiKey: ITZCJIBHWKEYAQ-UHFFFAOYSA-N

物化性质

• 沸点：
  411.6±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.62
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trifluoro-methanesulfonic acid 1-butyl-3-chloro-2-oxo-1,2-dihydropyridin-4-yl ester 、 4-[3-fluoro-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2-methylpyridine 在 四(三苯基膦)钯 碳酸氢钠 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.17h， 以7.5%的产率得到1-butyl-3-chloro-4-[2-fluoro-4-(2-methylpyridin-4-yloxy)phenyl]-1H-pyridin-2-one
  参考文献：
  名称：

  [EN] 1,3-DISUBSTITUTED 4-(ARYL-X-PHENYL)-1H-PYRIDIN-2-ONES
  [FR] 4-(ARYL-X-PHÉNYL)-1H-PYRIDINE-2-ONES 1,3-DISUBSTITUÉES

  摘要：

  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。

  公开号：

  WO2009033702A1
• 作为产物：
  描述：

  4-溴-3-氟苯酚 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 4-[3-fluoro-4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2-methylpyridine
  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。
• 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.