tert-butyl (2R,5R)-5-[(4-cyanopyridin-2-yl)oxy]-2-methylpiperidine-1-carboxylate | 1431473-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (2R,5R)-5-[(4-cyanopyridin-2-yl)oxy]-2-methylpiperidine-1-carboxylate
• 英文别名: tert-Butyl (2R,5R)-5-[(4-cyanopyridin-2-yl)oxy]-2-methylpiperidine-1-carboxylate；tert-butyl (2R,5R)-5-(4-cyanopyridin-2-yl)oxy-2-methylpiperidine-1-carboxylate
• CAS: 1431473-06-1
• 化学式: C₁₇H₂₃N₃O₃
• 分子量: 317.388
• InChiKey: DVYDQTOUZZRHRF-TZMCWYRMSA-N

物化性质

• 沸点：
  423.5±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  75.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R,5R)-5-[(4-cyanopyridin-2-yl)oxy]-2-methylpiperidine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 2-{[(3R,6R)-6-methyl-1-[(2-pyrimidin-2-ylphenyl)carbonyl]piperidin-3-yl]oxy}pyridine-4-carbonitrile
  参考文献：
  名称：

  2-PYRIDYLOXY-4-NITRILE OREXIN RECEPTOR ANTAGONISTS

  摘要：

  本发明涉及2-吡啶氧基-4-腈基化合物，其是促进睡眠荷尔蒙受体的拮抗剂。本发明还涉及使用本文所述的2-吡啶氧基-4-腈基化合物治疗或预防神经和精神障碍和疾病，这些疾病涉及到促进睡眠荷尔蒙受体。本发明还涉及包含这些化合物的制药组合物。本发明还涉及使用这些制药组合物预防或治疗涉及促进睡眠荷尔蒙受体的疾病。

  公开号：

  US20130102619A1
• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 盐酸 、 platinum(IV) oxide 、 锂硼氢 、 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 sodium hydroxide 、 偶氮二甲酸二乙酯 、 4-(二甲氨基)三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， -78.0~70.0 ℃ 、344.75 kPa 条件下， 反应 1.08h， 生成 tert-butyl (2R,5R)-5-[(4-cyanopyridin-2-yl)oxy]-2-methylpiperidine-1-carboxylate
  参考文献：
  名称：

  2-PYRIDYLOXY-4-NITRILE OREXIN RECEPTOR ANTAGONISTS

  摘要：

  本发明涉及2-吡啶氧基-4-腈基化合物，其是促进睡眠荷尔蒙受体的拮抗剂。本发明还涉及使用本文所述的2-吡啶氧基-4-腈基化合物治疗或预防神经和精神障碍和疾病，这些疾病涉及到促进睡眠荷尔蒙受体。本发明还涉及包含这些化合物的制药组合物。本发明还涉及使用这些制药组合物预防或治疗涉及促进睡眠荷尔蒙受体的疾病。

  公开号：

  US20130102619A1

文献信息

• Investigation of orexin-2 selective receptor antagonists: Structural modifications resulting in dual orexin receptor antagonists
  作者：Jason W. Skudlarek、Christina N. DiMarco、Kerim Babaoglu、Anthony J. Roecker、Joseph G. Bruno、Mark A. Pausch、Julie A. O'Brien、Tamara D. Cabalu、Joanne Stevens、Joseph Brunner、Pamela L. Tannenbaum、W. Peter Wuelfing、Susan L. Garson、Steven V. Fox、Alan T. Savitz、Charles M. Harrell、Anthony L. Gotter、Christopher J. Winrow、John J. Renger、Scott D. Kuduk、Paul J. Coleman

  DOI：10.1016/j.bmcl.2017.02.012

  日期：2017.3

  ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX2R subtype and culminating in the discovery of 23, a highly potent, OX2R-selective molecule that exhibited a promising in vivo profile. Further structural modification led to an unexpected restoration

  在探索使用orexin受体拮抗剂治疗失眠的持续努力中，对双重orexin受体拮抗剂（DORA）进行了结构修饰，从而产生了对OX2R亚型具有选择性的化合物，最终发现了23种高效能的OX2R选择性分子表现出有希望的体内轮廓。进一步的结构修饰导致OX1R拮抗作用的意外恢复。本文讨论了这些变化，并提出了基于计算建模的选择性原理。
• 2-pyridyloxy-4-nitrile orexin receptor antagonists
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US09156819B2

  公开（公告）日：2015-10-13

  The present invention is directed to 2-pyridyloxy-4-nitrile compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyl-oxy-4-nitrile compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及2-吡啶氧基-4-腈类化合物，其为促进醒觉素受体的拮抗剂。本发明还涉及使用本文所述的2-吡啶氧基-4-腈类化合物在治疗或预防涉及促进醒觉素受体的神经和精神障碍和疾病方面的应用。本发明还涉及包含这些化合物的制药组合物。本发明还涉及使用这些制药组合物在预防或治疗涉及促进醒觉素受体的这些疾病方面的应用。
• US9156819B2
  申请人：——

  公开号：US9156819B2

  公开（公告）日：2015-10-13
• [EN] 2-PYRIDYLOXY-4-NITRILE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE À BASE DE 2-PYRYDYLOXY-4-NITRILE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013059222A1

  公开（公告）日：2013-04-25

  The present invention is directed to 2-pyridyloxy-4-nitrile compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyl-oxy-4-nitrile compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orextn receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
• 2-PYRIDYLOXY-4-NITRILE OREXIN RECEPTOR ANTAGONISTS
  申请人：Kuduk Scott D.

  公开号：US20130102619A1

  公开（公告）日：2013-04-25

  The present invention is directed to 2-pyridyloxy-4-nitrile compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the 2-pyridyl-oxy-4-nitrile compounds described herein in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及2-吡啶氧基-4-腈基化合物，其是促进睡眠荷尔蒙受体的拮抗剂。本发明还涉及使用本文所述的2-吡啶氧基-4-腈基化合物治疗或预防神经和精神障碍和疾病，这些疾病涉及到促进睡眠荷尔蒙受体。本发明还涉及包含这些化合物的制药组合物。本发明还涉及使用这些制药组合物预防或治疗涉及促进睡眠荷尔蒙受体的疾病。