3,5-diphenylpyridin-2(1H)-one | 49667-34-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3,5-diphenylpyridin-2(1H)-one
• 英文别名: 3,5-Diphenyl-2-pyridon；3,5-diphenylpyridin-2-one；3,5-diphenyl-1H-pyridin-2-one；3,5-diphenyl-1H-pyridin-2-one
• CAS: 49667-34-7
• 化学式: C₁₇H₁₃NO
• 分子量: 247.296
• InChiKey: WTYAKBPRNHJPLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3,5-diphenylpyridin-2(1H)-one 、 苯硼酸 在 吡啶 、 氧气 、 copper diacetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以32%的产率得到1,3,5-Triphenylpyridin-2-one
  参考文献：
  名称：

  Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): A Novel, Noncompetitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) Receptor Antagonist

  摘要：

  Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.

  DOI：

  10.1021/jm301268u
• 作为产物：
  描述：

  2,3,5-三溴吡啶 在 potassium phosphate 、 四(三苯基膦)钯 、 氢溴酸 、 sodium methylate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 5.0h， 生成 3,5-diphenylpyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): A Novel, Noncompetitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) Receptor Antagonist

  摘要：

  Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.

  DOI：

  10.1021/jm301268u

文献信息

• Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of 3,5-Disubstituted Pyridines: Mechanistic Studies
  作者：Ta-Hsien Chuang、Yu-Chi Chen、Someshwar Pola

  DOI：10.1021/jo101394c

  日期：2010.10.1

  A series of disubstituted pyridine derivatives was synthesized from the corresponding acryloyl azides by acetic acid-promoted cycloaddition. This represents a novel and convenient synthetic approach to the symmetric 3,5-disubstituted pyridines. The nature of the substituent on the double bond and the utilized solvent were found to be crucial to the yield of pyridines. The reactivity of the acid-promoted

  通过乙酸促进的环加成反应，由相应的丙烯酰基叠氮化物合成了一系列双取代的吡啶衍生物。这代表了对称的3，5-二取代吡啶的新颖且方便的合成方法。发现双键上取代基的性质和所用溶剂对吡啶的产率至关重要。酸促进的环加成反应的反应性随芳基（例如苯基和吡啶基）的存在而增加。我们还通过13 C标记的肉桂酰叠氮化物的酸促进的环加成反应探索了全面的机理。由丙烯酰基叠氮化物通过乙酸促进的三分子缩合合成对称的3，5-二取代的吡啶。
• Synthesis of Trisubstituted Pyridines<i>via</i>Chemoselective Suzuki-Miyaura Coupling of 3,5- and 4,6-Dibromo-2-tosyloxypyridines
  作者：Cho-Hee Park、Yong-Ju Kwon、In-Young Oh、Won-Suk Kim

  DOI：10.1002/adsc.201600950

  日期：2017.1.4

  diarylpyridine derivatives obtained was accomplished for the synthesis of novel and biologically relevant trisubstituted pyridines. The formal synthesis of ficuseptine, a bioactive alkaloid, has also been achieved via the palladium‐catalyzed cross‐coupling reaction of 3,5‐dibromo‐2‐tosyloxypyridine in 5 steps from 3,5‐dibromo‐2‐hydroxypyridine with 50% overall yield.

  已经研究了对3,5-和4,6-二溴-2-甲苯磺酰氧吡啶的化学选择性Suzuki-Miyaura反应，用于制备三取代的吡啶。优化的条件使得可以轻松获得3,5-和4,6-二芳基-2-甲苯磺酰氧吡啶，产率为8％至99％。进一步的功能化，如钯催化的胺化反应和所获得的二芳基吡啶衍生物中甲苯磺酸酯基团的无铜Sonogashira反应，可用于合成新型的和生物学上相关的三取代的吡啶。通过3,5-二溴-2-甲苯磺酰氧基吡啶在3,5-二溴-2-羟基吡啶的5个步骤中钯催化的交叉偶联反应也已完成了具有生物活性的生物碱生物碱的正式合成。屈服。
• Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (Perampanel): A Novel, Noncompetitive α-Amino-3-hydroxy-5-methyl-4-isoxazolepropanoic Acid (AMPA) Receptor Antagonist
  作者：Shigeki Hibi、Koshi Ueno、Satoshi Nagato、Koki Kawano、Koichi Ito、Yoshihiko Norimine、Osamu Takenaka、Takahisa Hanada、Masahiro Yonaga

  DOI：10.1021/jm301268u

  日期：2012.12.13

  Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.