3-(benzyloxy)-5-(4-methoxyphenyl)-6-(pyridin-4-yl)-1-methyl-1H-pyridin-2-one | 216970-81-9

• 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-(benzyloxy)-5-(4-methoxyphenyl)-6-(pyridin-4-yl)-1-methyl-1H-pyridin-2-one
• 英文别名: 3-(benzyloxy)-5-(4-methoxyphenyl)-6-(4-pyridyl)-1-methyl-1H-pyridin-2-one；3-(4-Methoxyphenyl)-1-methyl-5-(phenylmethoxy)-[2,4'-bipyridin]-6(1h)-one；5-(4-methoxyphenyl)-1-methyl-3-phenylmethoxy-6-pyridin-4-ylpyridin-2-one
• CAS: 216970-81-9
• 化学式: C₂₅H₂₂N₂O₃
• 分子量: 398.461
• InChiKey: XJMAYTXFDJPGRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-(4-methoxyphenyl)-6-(pyridin-4-yl)-1-methyl-1H-pyridin-2-one 在 10percent Pd/C 吡啶 、 甲酸铵 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 3-trifluoromethanesulfonyl-5-(4-methoxyphenyl)-6-(4-pyridyl)-1-methyl-1H-pyridin-2-one
  参考文献：
  名称：

  3-Heteroaryl-2-pyridones:  Benzodiazepine Site Ligands with Functional Selectivity for α2/α3-Subtypes of Human GABA_A Receptor-Ion Channels

  摘要：

  A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha2- and/or alpha3- over alpha1-containing GABA(A) receptor subtypes and high binding selectivity over alpha5 subtypes. High affinity appeared to be associated with a coplanar conformation of the pyridone and sulfur-containing 3-heteroaryl rings resulting from an attractive S...O intramolecular interaction. Functional selectivity (i.e., selective efficacy) for alpha2 and/or alpha3 GABA(A) receptor subtypes over alpha1 was observed in several of these compounds in electrophysiological assays. Furthermore, an alpha3 subtype selective inverse agonist was proconvulsant and anxiogenic in rodents while an alpha2/alpha3 subtype selective partial agonist was anticonvulsant and anxiolytic, supporting the hypothesis that subtype selective BZ site agonists may provide new anxiolytic therapies.

  DOI：

  10.1021/jm0110789
• 作为产物：
  描述：

  1-isonicotinoyl-1H-imidazole 在 四氯化钛 、 sodium chloride 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 24.33h， 生成 3-(benzyloxy)-5-(4-methoxyphenyl)-6-(pyridin-4-yl)-1-methyl-1H-pyridin-2-one
  参考文献：
  名称：

  3-Heteroaryl-2-pyridones:  Benzodiazepine Site Ligands with Functional Selectivity for α2/α3-Subtypes of Human GABA_A Receptor-Ion Channels

  摘要：

  A novel series of 3-heteroaryl-5,6-bis(aryl)-1-methyl-2-pyridones were developed with high affinity for the benzodiazepine (BZ) binding site of human gamma-aminobutyric acid (GABA(A)) receptor ion channels, low binding selectivity for alpha2- and/or alpha3- over alpha1-containing GABA(A) receptor subtypes and high binding selectivity over alpha5 subtypes. High affinity appeared to be associated with a coplanar conformation of the pyridone and sulfur-containing 3-heteroaryl rings resulting from an attractive S...O intramolecular interaction. Functional selectivity (i.e., selective efficacy) for alpha2 and/or alpha3 GABA(A) receptor subtypes over alpha1 was observed in several of these compounds in electrophysiological assays. Furthermore, an alpha3 subtype selective inverse agonist was proconvulsant and anxiogenic in rodents while an alpha2/alpha3 subtype selective partial agonist was anticonvulsant and anxiolytic, supporting the hypothesis that subtype selective BZ site agonists may provide new anxiolytic therapies.

  DOI：

  10.1021/jm0110789

文献信息

• A convenient synthesis of highly substituted 2-pyridones
  作者：Ian Collins、JoséL. Castro

  DOI：10.1016/s0040-4039(99)00651-6

  日期：1999.5

  first examples of this class of compound, was achieved by Vilsmeier formylation and cyclisation of the acyl enamine 6. The triflate 2 was found to undergo a range of palladium-catalysed coupling reactions giving a synthetic sequence of general use for the preparation of highly substituted 2-pyridones.

  通过维斯迈尔甲酰化和酰基烯胺6的环化反应，可以快速方便地合成3-三氟甲磺酰氧基-2-吡啶酮2，这类化合物的第一个例子。发现三氟甲磺酸酯2经历了一系列钯催化的偶联反应，给出了通常用于制备高度取代的2-吡啶酮的合成序列。
• Substituted 1H-pyridinyl-2-ones as GABAA alpha 2/3 ligands
  申请人：Merck Sharp & Dohme Limited

  公开号：US06352994B2

  公开（公告）日：2002-03-05

  Compounds according to Formula (I) or a salt thereof are selective ligands for GABAA receptors useful for treatment of disorders of the central nervous system:

  根据式（I）的化合物或其盐是选择性的GABAA受体配体，用于治疗中枢神经系统疾病。
• Substituted 1H-pyridinyl-2-ones as GABAA-&agr; 2/3 ligands
  申请人：Merck & Dohme Limited

  公开号：US06200982B1

  公开（公告）日：2001-03-13

  Substituted 1H-Pyridinyl-2-ones are useful as GABAA-Alpha 2/3 ligands.

  取代的1H-吡啶基-2-酮可作为GABAA-Alpha 2/3配体。
• SUBSTITUTED 1H-PYRIDINYL-2-ONES AS GABA A?ALPHA 2/3 LIGANDS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0994873A1

  公开（公告）日：2000-04-26
• US6200982B1
  申请人：——

  公开号：US6200982B1

  公开（公告）日：2001-03-13