(4S)-4-(4-fluorophenyl)-N-[5-[4-[(2R)-2-hydroxy-3-methoxy-propyl]-3,5-dioxo-1,2,4-triazin-2-yl]-2-methyl-phenyl]-1-methyl-2-oxo-3,4-dihydropyridine-5-carboxamide | 1232890-10-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4S)-4-(4-fluorophenyl)-N-[5-[4-[(2R)-2-hydroxy-3-methoxy-propyl]-3,5-dioxo-1,2,4-triazin-2-yl]-2-methyl-phenyl]-1-methyl-2-oxo-3,4-dihydropyridine-5-carboxamide
• 英文别名: (S)-4-(4-fluoro-phenyl)-1-methyl-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {5-[4-((R)-2-hydroxy-3-methoxy-propyl)-3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl]-2-methyl-phenyl}-amide；(4S)-4-(4-fluorophenyl)-N-[5-[4-[(2R)-2-hydroxy-3-methoxypropyl]-3,5-dioxo-1,2,4-triazin-2-yl]-2-methylphenyl]-1-methyl-2-oxo-3,4-dihydropyridine-5-carboxamide
• CAS: 1232890-10-6
• 化学式: C₂₇H₂₈FN₅O₆
• 分子量: 537.548
• InChiKey: AXCQGTYDWZDCCM-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (4S)-4-(4-fluorophenyl)-1-methyl-2-oxo-3,4-dihydropyridine-5-carboxylic acid 、 2-(3-amino-4-methylphenyl)-4-[(2R)-2-hydroxy-3-methoxy-propyl]-1,2,4-triazine-3,5-dione 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 18.5h， 以39%的产率得到(4S)-4-(4-fluorophenyl)-N-[5-[4-[(2R)-2-hydroxy-3-methoxy-propyl]-3,5-dioxo-1,2,4-triazin-2-yl]-2-methyl-phenyl]-1-methyl-2-oxo-3,4-dihydropyridine-5-carboxamide
  参考文献：
  名称：

  Novel Series of Dihydropyridinone P2X7 Receptor Antagonists

  摘要：

  Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5", and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.

  DOI：

  10.1021/acs.jmedchem.5b00365

文献信息

• DIHYDROPYRIDONE AMIDES AS P2X7 MODULATORS
  申请人：Berger Jacob

  公开号：US20100160384A1

  公开（公告）日：2010-06-24

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, p, q, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.

  化合物的公式I：或其药用盐，其中m、n、p、q、R1、R2、R3、R4、R5和R6如本文所定义。还公开了制备这些化合物的方法，并将这些化合物用于治疗与P2X7嘌呤受体相关的疾病。
• US8163929B2
  申请人：——

  公开号：US8163929B2

  公开（公告）日：2012-04-24
• [EN] DIHYDROPYRIDONE AMIDES AS P2X7 MODULATORS<br/>[FR] AMIDES DE DIHYDROPYRIDONE UTILES COMME MODULATEURS DE P2X7
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010072607A1

  公开（公告）日：2010-07-01

  Compounds of the formula (I) or pharmaceutically acceptable salts thereof, wherein m, n, p, q, R1, R2, R3, R4, R5 and R6 are as defined herein. Also disclosed are methods of making the compounds and using the compounds for treatment of diseases associated with the P2X7 purinergic receptor.
• Novel Series of Dihydropyridinone P2X7 Receptor Antagonists
  作者：Francisco Lopez-Tapia、Keith A. M. Walker、Christine Brotherton-Pleiss、Joanie Caroon、Dov Nitzan、Lee Lowrie、Shelley Gleason、Shu-Hai Zhao、Jacob Berger、Debra Cockayne、Deborah Phippard、Rebecca Suttmann、William L. Fitch、David Bourdet、Pankaj Rege、Xiaojun Huang、Scott Broadbent、Charles Dvorak、Jiang Zhu、Paul Wagner、Fernando Padilla、Brad Loe、Alam Jahangir、André Alker

  DOI：10.1021/acs.jmedchem.5b00365

  日期：2015.11.12

  Identification of singleton P2X7 inhibitor 1 from HTS gave a pharmacophore that eventually turned into potential clinical candidates 17 and 19. During development, a number of issues were successfully addressed, such as metabolic stability, plasma stability, GSH adduct formation, and aniline mutagenicity. Thus, careful modification of the molecule, such as conversion of the 1,4-dihydropyridinone to the 1,2-dihydropyridinone system, proper substitution at C-5", and in some cases addition of fluorine atoms to the aniline ring allowed for the identification of a novel class of potent P2X7 inhibitors suitable for evaluating the role of P2X7 in inflammatory, immune, neurologic, or musculoskeletal disorders.