1,5-diphenylpyridin-2(1H)-one

• 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: 1,5-diphenylpyridin-2(1H)-one
• 英文别名: 1,5-Diphenylpyridin-2-one
• 化学式: C₁₇H₁₃NO
• 分子量: 247.296
• InChiKey: ILGWLGABMQLRFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 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：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,5-diphenylpyridin-2(1H)-one 、 二苯基乙炔 在 dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer 、 silver(l) oxide 、 双三氟甲烷磺酰亚胺银盐 、 三甲基乙酸 作用下， 以 1,2-二氯乙烷 为溶剂， 以89 %的产率得到5-phenyl-1-(5,6,7,8-tetraphenylnaphthalen-1-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  Rh(III)-催化的弱配位 2-吡啶酮定向氧化环化使用内部炔烃：选择性的逆转

  摘要：

  使用内部炔烃作为偶联伙伴描述了N -芳基 2-吡啶酮衍生物的铑 (III) 催化的 Satoh-Miura 型氧化环化。2-吡啶酮环的弱配位羰基用于该转化。反应进行范围广，官能团宽容。溶剂在提供不同类别环状产品的开发方法中起着重要作用。进行了初步研究以探索所获得的多芳基化N-萘基 2-吡啶酮的光物理性质。

  DOI：

  10.1021/acs.orglett.2c03187
• 作为产物：
  描述：

  5-溴-2-甲氧基吡啶 在 四(三苯基膦)钯 、 氢溴酸 、 potassium acetate 、 铜 、 sodium carbonate 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 6.5h， 生成 1,5-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

• COMPOUNDS AND METHODS FOR TREATING INFLAMMATORY AND FIBROTIC DISORDERS
  申请人：Kossen Karl

  公开号：US20090318455A1

  公开（公告）日：2009-12-24

  Disclosed are compounds and methods for treating inflammatory and fibrotic disorders, including methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of the p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the p38 MAPK by the compound. Also disclosed are derivatives and analogs of pirfenidone, useful for modulating a stress activated protein kinase (SAPK) system.

  公开了用于治疗炎症和纤维化疾病的化合物和方法，包括用活性化合物调节应激活化蛋白激酶（SAPK）系统的方法，其中活性化合物对p38 MAPK的抑制效力较低；并且其中接触是在SAPK调节浓度下进行的，该浓度对化合物抑制p38 MAPK的抑制浓度百分比较低。还公开了吡非尼酮的衍生物和类似物，它们可用于调节应激活化蛋白激酶（SAPK）系统。
• A highly efficient Suzuki–Miyaura methylation of pyridines leading to the drug pirfenidone and its CD₃ version (SD-560)
  作者：Eliezer Falb、Konstantin Ulanenko、Andrey Tor、Ronen Gottesfeld、Michal Weitman、Michal Afri、Hugo Gottlieb、Alfred Hassner

  DOI：10.1039/c7gc01740e

  日期：——

  Efficient introduction of methyl or methyl-d3 into aromatic and heteroaromatic systems still presents a synthetic challenge. In particular, we were in search of a non-cryogenic synthesis of the 5-CD3 version of pirfenidone (4d, also known as Pirespa®, Esbriet® or Pirfenex®), one of the two drugs approved to date for retarding idiopathic pulmonary fibrosis (IPF), a serious, rare and fatal lung disease

  有效地将甲基或甲基-d3引入芳族和杂芳族体系仍然是一个合成难题。尤其是，我们正在寻找非CD3形式的吡非尼酮（4d，也称为Pirespa®，Esbriet®或Pirfenex®）的非低温合成方法，这是迄今为止批准的用于延迟特发性肺纤维化的两种药物之一（IPF），一种严重，罕见和致命的肺部疾病，预期寿命为3-5年。甲基氘代吡非尼酮（4e，也称为SD-560）的设计旨在降低药物代谢速率，我们的目标是找到一条绿色的甲基化途径，以避免使用烷基锂对环境和经济的影响在低温下。在RuPhos配体存在下，研究将甲基或甲基d3引入甲氧基吡啶和吡啶酮体系的几种交叉偶联策略，最终以两种绿色且几乎定量的Suzuki-Miyaura交叉偶联途径完成：第一种，使用可商购的甲基硼酸或其CD3类似物；第二种是使用三氟硼酸钾钾或CD3BF3K，后者通过新途径获得，收率为88％。这导致了几十克的吡非尼酮（4d）及其d3类似物S
• Methods of Treating Atrial Fibrillation with P38 Inhibitor Compounds
  申请人：Olgin Jeff

  公开号：US20100029578A1

  公开（公告）日：2010-02-04

  The invention disclosed herein relates generally to compounds and methods useful in treating or preventing atrial fibrillation (AF).

  本发明涉及通常用于治疗或预防房颤(AF)的化合物和方法。
• METHODS OF TREATING ATRIAL FIBRILLATION WITH P38 INHIBITOR COMPOUNDS
  申请人：Olgin Jeff

  公开号：US20120046321A1

  公开（公告）日：2012-02-23

  The invention disclosed herein relates generally to compounds and methods useful in treating or preventing atrial fibrillation (AF).

  本发明涉及一般与化合物和方法有关，用于治疗或预防心房颤动（AF）。
• METHOD OF MODULATING STRESS-ACTIVATED PROTEIN KINASE SYSTEM
  申请人：Blatt Lawrence M.

  公开号：US20120258924A1

  公开（公告）日：2012-10-11

  Disclosed are methods of modulating a stress activated protein kinase (SAPK) system with an active compound, wherein the active compound exhibits low potency for inhibition of at least one p38 MAPK; and wherein the contacting is conducted at a SAPK-modulating concentration that is at a low percentage inhibitory concentration for inhibition of the at least one p38 MAPK by the compound. Also disclosed are derivatives of pirfenidone. These derivatives can modulate a stress activated protein kinase (SAPK) system.

  本发明涉及使用活性化合物调节应激激活蛋白激酶（SAPK）系统的方法，其中该活性化合物对至少一种p38 MAPK抑制的效力较低；并且该接触是在该化合物对至少一种p38 MAPK的抑制浓度低百分比的SAPK调节浓度下进行的。本发明还涉及吡非尼酮的衍生物，这些衍生物可以调节应激激活蛋白激酶（SAPK）系统。