3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2,6-dimethylpyridine | 1362703-34-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2,6-dimethylpyridine
• 英文别名: 2,6-Dimethyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]pyridine
• CAS: 1362703-34-1
• 化学式: C₁₉H₂₄BNO₃
• 分子量: 325.215
• InChiKey: LHDZWDMKQAJVHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.79
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-溴-1-丁基-2-氧代-1,2-二氢吡啶-3-腈 、 3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-2,6-dimethylpyridine 在 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.17h， 以65%的产率得到1-butyl-4-[4-(2,6-dimethylpyridin-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-(4-nitrophenoxy)-2,6-dimethylpyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 potassium acetate 、 sodium nitrite 作用下， 以 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 7.0h， 生成 3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenoxy]-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