3-carbethoxy-1,6-diphenyl-4(1H)-pyridinone | 134653-95-5

• 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-carbethoxy-1,6-diphenyl-4(1H)-pyridinone
• 英文别名: ethyl 4-oxo-1,6-diphenyl-1,4-dihydropyridine-3-carboxylate；Ethyl 4-oxo-1,6-diphenylpyridine-3-carboxylate
• CAS: 134653-95-5
• 化学式: C₂₀H₁₇NO₃
• 分子量: 319.36
• InChiKey: HWENOVCBKAFROD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-carbethoxy-1,6-diphenyl-4(1H)-pyridinone 在 sodium hydroxide 、 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以94%的产率得到4-oxo-1,6-diphenyl-1,4-dihydropyridine-3-carboxylic acid
  参考文献：
  名称：

  4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series

  摘要：

  Growing evidence shows that CB2 receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective CB2 agonists, we describe here the medicinal chemistry approach leading to the development of CB2 receptor inverse agonists with a 4-oxo-1,4-dihydropyridine scaffold. The compounds reported here show high affinity and potency at the CB2, receptor while showing only modest affinity for the centrally expressed CB1 cannabinoid receptor. Further, we found that the functionality of this series is controlled by its C-6 substituent because agonists bear a methyl or a tert-butyl group and inverse agonists, a phenyl or 4-chlorophenyl group, respectively. Finally, in silico studies suggest that the C-6 substituent could modulate the conformation of W6.48 known to be critical in GPCR activation.

  DOI：

  10.1021/jm100286k
• 作为产物：
  描述：

  3-carbethoxy-6-phenyl-4-pyrone 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 2.25h， 生成 3-carbethoxy-1,6-diphenyl-4(1H)-pyridinone
  参考文献：
  名称：

  Generation and in situ acylation of enaminone anions: a convenient synthesis of 3-carbethoxy-4(1H)-pyridinones and -4-pyrones and related compounds

  摘要：

  Treatment of 2-[(dimethylamino)methylene]-3-oxobutanoates 9 or 10 with LiN(SiMe3)2 in the presence of RCOCl results in C-acylation. The resulting intermediate, without isolation, may be converted to 6-R 3-Carbethoxy-4-pyrones (e.g., 12) by H3O+ or to the corresponding pyridinones (e.g., 13) by NH4OAc. Typically, yields are 55-75% for R groups lacking acidic alpha or gamma protons and ca. 30% for R = Me2CH or MeCH = CH. Replacing 9 with MeCOC(= CHNMe2)SCH2Ph (from MeCOCH2SCH2Ph and Me2NCH(OMe)2 similarly affords 3(PhCH2S)-substituted products such as 29. Alkylation of the pyridinone anions produces mixtures of N- and O-substituted compounds, with the latter predominating; aminolysis of the isolated pyrones (R'NH2-HOAc, where R' = alkyl, Ar, HO, etc.) is the preferred route to the 1-R'-substituted pyridinones.

  DOI：

  10.1021/jo00016a028

文献信息

• [EN] 1,4 DIHYDROPYRIDINE DERIVATIVES AND THEIR USES<br/>[FR] DÉRIVÉS DE LA 1,4-DIHYDROPYRIDINE ET LEURS UTILISATIONS
  申请人：UNIV LILLE II DROIT & SANTE

  公开号：WO2010133973A1

  公开（公告）日：2010-11-25

  The present invention relates to 1,4-dihydropyridine derivatives of the formula (I) and their uses in the treatment and/or prevention of diseases and disorders directly or indirectly associated with the modification (increase or decrease) of the activity of the cannabinoid receptor 2 (CB2).

  本发明涉及式(I)的1,4-二氢吡啶衍生物及其在治疗和/或预防与大麻素受体2（CB2）的活性修改（增加或减少）直接或间接相关的疾病和紊乱中的用途。
• 1,4-Dihydropyridine Derivatives and Their Uses
  申请人：Millet Regis

  公开号：US20120149735A1

  公开（公告）日：2012-06-14

  The present invention relates to 1,4-dihydropyridine derivatives of the formula (I) and their uses in the treatment and/or prevention of diseases and disorders directly or indirectly associated with the modification (increase or decrease) of the activity of the cannabinoid receptor 2 (CB2).

  本发明涉及式（I）的1,4-二氢吡啶衍生物及其在治疗和/或预防与大麻素受体2（CB2）的活性调节（增加或减少）直接或间接相关的疾病和障碍方面的用途。
• 1,4-dihydropyridine derivatives and their uses
  申请人：Université de Lille 2 Droit et Santé

  公开号：EP2261211A1

  公开（公告）日：2010-12-15

  The present invention relates to 1,4-dihydropyridine derivatives of the formula (I) and their uses in the treatment and/or prevention of diseases and disorders directly or indirectly associated with the modification (increase or decrease) of the activity of the cannabinoid receptor 2 (CB2).

  本发明涉及式（I）的 1,4-二氢吡啶衍生物及其在治疗和/或预防与大麻素受体 2（CB2）活性改变（增加或降低）直接或间接相关的疾病和失调中的用途。
• 4-Oxo-1,4-dihydropyridines as Selective CB₂ Cannabinoid Receptor Ligands: Structural Insights into the Design of a Novel Inverse Agonist Series
  作者：Jamal El Bakali、Giulio G. Muccioli、Nicolas Renault、Delphine Pradal、Mathilde Body-Malapel、Madjid Djouina、Laurie Hamtiaux、Virginie Andrzejak、Pierre Desreumaux、Philippe Chavatte、Didier M. Lambert、Régis Millet

  DOI：10.1021/jm100286k

  日期：2010.11.25

  Growing evidence shows that CB2 receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide as selective CB2 agonists, we describe here the medicinal chemistry approach leading to the development of CB2 receptor inverse agonists with a 4-oxo-1,4-dihydropyridine scaffold. The compounds reported here show high affinity and potency at the CB2, receptor while showing only modest affinity for the centrally expressed CB1 cannabinoid receptor. Further, we found that the functionality of this series is controlled by its C-6 substituent because agonists bear a methyl or a tert-butyl group and inverse agonists, a phenyl or 4-chlorophenyl group, respectively. Finally, in silico studies suggest that the C-6 substituent could modulate the conformation of W6.48 known to be critical in GPCR activation.
• Generation and in situ acylation of enaminone anions: a convenient synthesis of 3-carbethoxy-4(1H)-pyridinones and -4-pyrones and related compounds
  作者：Stuart W. McCombie、William A. Metz、Dennis Nazareno、Bandarpalle B. Shankar、Jayaram Tagat

  DOI：10.1021/jo00016a028

  日期：1991.8

  Treatment of 2-[(dimethylamino)methylene]-3-oxobutanoates 9 or 10 with LiN(SiMe3)2 in the presence of RCOCl results in C-acylation. The resulting intermediate, without isolation, may be converted to 6-R 3-Carbethoxy-4-pyrones (e.g., 12) by H3O+ or to the corresponding pyridinones (e.g., 13) by NH4OAc. Typically, yields are 55-75% for R groups lacking acidic alpha or gamma protons and ca. 30% for R = Me2CH or MeCH = CH. Replacing 9 with MeCOC(= CHNMe2)SCH2Ph (from MeCOCH2SCH2Ph and Me2NCH(OMe)2 similarly affords 3(PhCH2S)-substituted products such as 29. Alkylation of the pyridinone anions produces mixtures of N- and O-substituted compounds, with the latter predominating; aminolysis of the isolated pyrones (R'NH2-HOAc, where R' = alkyl, Ar, HO, etc.) is the preferred route to the 1-R'-substituted pyridinones.