(4S)-N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-methyl-indazol-6-yl]-4-(4-fluorophenyl)-2-oxo-3,4-dihydro-1H-pyridine-5-carboxamide | 1232685-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: (4S)-N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-methyl-indazol-6-yl]-4-(4-fluorophenyl)-2-oxo-3,4-dihydro-1H-pyridine-5-carboxamide
• 英文别名: (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-5-methyl-1H-indazol-6-yl}-amide；(4S)-N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-methylindazol-6-yl]-4-(4-fluorophenyl)-2-oxo-3,4-dihydro-1H-pyridine-5-carboxamide
• CAS: 1232685-21-0
• 化学式: C₂₈H₃₅FN₄O₃Si
• 分子量: 522.695
• InChiKey: YMNLEPYDZLIFHV-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.63
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4S)-N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-methyl-indazol-6-yl]-4-(4-fluorophenyl)-2-oxo-3,4-dihydro-1H-pyridine-5-carboxamide 在 methanol-dichloromethane 作用下， 以 溶剂黄146 、 水 、 四氢呋喃 为溶剂， 反应 16.0h， 以to give 24 mg (70.6%) of (S)-4-(4-Fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid [1-(2-hydroxy-ethyl)-5-methyl-1H-indazol-6-yl]-amide white crystalline solid的产率得到(4S)-4-(4-fluorophenyl)-N-[1-(2-hydroxyethyl)-5-methyl-indazol-6-yl]-2-oxo-3,4-dihydro-1H-pyridine-5-carboxamide
  参考文献：
  名称：

  DIHYDROPYRIDONE AMIDES AS P2X7 MODULATORS

  摘要：

  本发明涉及化合物I的制备方法，或其药学上可接受的盐，其中m、n、R1、R2、R3、R4、R5和Ra的定义如本文所述。还公开了制备该化合物的方法，并使用该化合物治疗与P2X7嘌呤能受体相关的疾病的方法。

  公开号：

  US20100160373A1
• 作为产物：
  描述：

  (R)-3-(4-fluorophenyl)-2-formylpentanedioic acid 1-methyl ester 在 吡啶 、 4-二甲氨基吡啶 、 ammonium acetate 、 溶剂黄146 、 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 (4S)-N-[1-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-5-methyl-indazol-6-yl]-4-(4-fluorophenyl)-2-oxo-3,4-dihydro-1H-pyridine-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：US20100160373A1

  公开（公告）日：2010-06-24

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, R 1 , R 2 , R 3 , R 4 , R 5 and R a 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.

  公式I的化合物：或其药用盐，其中m，n，R1，R2，R3，R4，R5和Ra如本文所定义。还公开了制备这些化合物的方法以及利用这些化合物治疗与P2X7嘌呤受体相关的疾病的方法。
• Dihydropyridone amides as P2X7 modulators
  申请人：Berger Jacob

  公开号：US08372865B2

  公开（公告）日：2013-02-12

  Compounds of the formula I: or pharmaceutically acceptable salts thereof, wherein m, n, R1, R2, R3, R4, R5 and Ra 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.

  化合物的公式为I：或其药学上可接受的盐，其中m，n，R1，R2，R3，R4，R5和Ra的定义如本文所述。还公开了制备该化合物的方法，并使用该化合物治疗与P2X7嘌呤能受体相关的疾病。
• 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.