1-O-tert-butyl 5-O-methyl 4-naphthalen-2-yl-3,6-dihydro-2H-pyridine-1,5-dicarboxylate | 916149-72-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1-O-tert-butyl 5-O-methyl 4-naphthalen-2-yl-3,6-dihydro-2H-pyridine-1,5-dicarboxylate
• CAS: 916149-72-9
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: PLIANOMOCLSKOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-O-tert-butyl 5-O-methyl 4-naphthalen-2-yl-3,6-dihydro-2H-pyridine-1,5-dicarboxylate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 0.27h， 生成 tert-butyl 5-(hydroxymethyl)-4-naphthalen-2-yl-3,6-dihydro-2H-pyridine-1-carboxylate
  参考文献：
  名称：

  6-(3,4-Dichlorophenyl)-1-[(Methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: A New Potent and Selective Triple Reuptake Inhibitor

  摘要：

  A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characteristics. Excellent bioavailability and brain penetration are associated with this series of 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together with high in vitro potency and selectivity at SERT, NET, and DAT. In vivo microdialysis experiments in different animal models and receptor occupancy studies in rat confirmed that derivative 17 showed an appropriate profile to further progression of the compound.

  DOI：

  10.1021/jm100481d
• 作为产物：
  描述：

  1-tert-butyl 3-methyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1,3(2H)-dicarboxylate 、 2-萘硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 1.0h， 生成 1-O-tert-butyl 5-O-methyl 4-naphthalen-2-yl-3,6-dihydro-2H-pyridine-1,5-dicarboxylate
  参考文献：
  名称：

  6-(3,4-Dichlorophenyl)-1-[(Methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: A New Potent and Selective Triple Reuptake Inhibitor

  摘要：

  A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characteristics. Excellent bioavailability and brain penetration are associated with this series of 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together with high in vitro potency and selectivity at SERT, NET, and DAT. In vivo microdialysis experiments in different animal models and receptor occupancy studies in rat confirmed that derivative 17 showed an appropriate profile to further progression of the compound.

  DOI：

  10.1021/jm100481d

文献信息

• Substituted Piperdines as Renin Inhibitors
  申请人：Ehara Takeru

  公开号：US20090137566A1

  公开（公告）日：2009-05-28

  The invention relates to substituted 3,4- or higher substituted piperididine compounds, the use thereof for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; pharmaceutical formulations or products comprising said compounds, and/or a method of treatment comprising administering said compounds, a method for the manufacture of said compounds, as well as novel intermediates, starting materials and/or partial steps for their synthesis. The compounds preferably have the formula I, wherein the moieties R1, R2, R11 and W are as defined in the specification.

  该发明涉及替代的3,4-或更高替代的哌啶基化合物，其用于制备用于治疗依赖肾素活性的疾病的药物配方；该类化合物在治疗依赖肾素活性的疾病中的应用；这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖肾素活性的疾病的治疗；包括上述化合物的药物配方或产品，以及/或包括上述化合物的给药方法，制备上述化合物的方法，以及用于其合成的新中间体、起始材料和/或部分步骤。这些化合物优选具有公式 I，其中基团 R1、R2、R11 和 W 如规范中所定义。
• [EN] SUBSTITUTED PIPERIDINES AS RENIN INHIBITORS<br/>[FR] PIPERIDINES SUBSTITUEES UTILISEES COMME INHIBITEURS DE LA RENINE
  申请人：NOVARTIS AG

  公开号：WO2006125621A1

  公开（公告）日：2006-11-30

  [EN] The invention relates to substituted 3,4- or higher substituted piperididine compounds, the use thereof for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (= disorder) that depends on activity of renin; pharmaceutical formulations or products comprising said compounds, and/or a method of treatment comprising administering said compounds, a method for the manufacture of said compounds, as well as novel intermediates, starting materials and/or partial steps for their synthesis. The compounds preferably have the formula I, wherein the moieties R1, R2, R11 and W are as defined in the specification.
  [FR] L'invention concerne des composés de pipéridine substitués à substitution 3,4 ou supérieure, leur utilisation pour la préparation d'une préparation pharmaceutique pour le traitement d'une maladie dépendant de l'activité de la rénine, l'utilisation d'un composé de cette catégorie dans le traitement d'une maladie dépendant de l'activité de la rénine, l'utilisation de ces composés à des fins diagnostiques ou thérapeutiques chez un animal à sang chaud, notamment pour traiter une maladie (= trouble) dépendant de l'activité de la rénine, des préparations ou des produits pharmaceutiques renfermant lesdits composés, et/ou une méthode de traitement consistant à administrer ces composés, un procédé de fabrication de ces composés, ainsi que de nouveaux produits intermédiaires, de nouvelles matières de départ et/ou des étapes partielles pour leur synthèse. De préférence, lesdits composés sont représentés par la formule (I), dans laquelle les fractions R1, R2, R11 et W sont telles que définies dans la description.
• 6-(3,4-Dichlorophenyl)-1-[(Methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: A New Potent and Selective Triple Reuptake Inhibitor
  作者：Fabrizio Micheli、Paolo Cavanni、Daniele Andreotti、Roberto Arban、Roberto Benedetti、Barbara Bertani、Michela Bettati、Letizia Bettelini、Giorgio Bonanomi、Simone Braggio、Renzo Carletti、Anna Checchia、Mauro Corsi、Elettra Fazzolari、Stefano Fontana、Carla Marchioro、Emilio Merlo-Pich、Michele Negri、Beatrice Oliosi、Emiliangelo Ratti、Kevin D. Read、Maja Roscic、Ilaria Sartori、Simone Spada、Giovanna Tedesco、Luca Tarsi、Silvia Terreni、Filippo Visentini、Alessandro Zocchi、Laura Zonzini、Romano Di Fabio

  DOI：10.1021/jm100481d

  日期：2010.7.8

  A pharmacophore model for triple reuptake inhibitors and the new class of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes were recently reported. Further investigation in this area led to the identification of a new series of potent and selective triple reuptake inhibitors endowed with good developability characteristics. Excellent bioavailability and brain penetration are associated with this series of 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptanes together with high in vitro potency and selectivity at SERT, NET, and DAT. In vivo microdialysis experiments in different animal models and receptor occupancy studies in rat confirmed that derivative 17 showed an appropriate profile to further progression of the compound.