2-{[(3R,6R)-6-methyl-1-{[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}piperidin-3-yl]oxy}pyridine-4-carbonitrile | 1431472-58-0

• 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: 2-{[(3R,6R)-6-methyl-1-{[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]carbonyl}piperidin-3-yl]oxy}pyridine-4-carbonitrile
• 英文别名: 2-[(3R,6R)-6-methyl-1-[2-(5-methyl-1,2,4-oxadiazol-3-yl)benzoyl]piperidin-3-yl]oxypyridine-4-carbonitrile
• CAS: 1431472-58-0
• 化学式: C₂₂H₂₁N₅O₃
• 分子量: 403.44
• InChiKey: DZHWCPHUSBPNJT-RHSMWYFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-羟基-6-甲基吡啶 在 盐酸 、 platinum(IV) oxide 、 锂硼氢 、 N-羟基-7-氮杂苯并三氮唑 、 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 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 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， -78.0~70.0 ℃ 、344.75 kPa 条件下， 反应 1.08h， 生成 2-{[(3R,6R)-6-methyl-1-{[2-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]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

文献信息

• Methods and pharmaceutical compositions for the treatment of cancer
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE)

  公开号：US10894042B2

  公开（公告）日：2021-01-19

  The present invention relates to methods and pharmaceutical compositions for the treatment of cancer. More particularly, the present invention relates to a method of treating cancer in subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one OX1R antagonist.

  本发明涉及治疗癌症的方法和药物组合物。更具体地说，本发明涉及一种治疗有需要的受试者癌症的方法，该方法包括向受试者施用治疗有效量的至少一种 OX1R 拮抗剂。
• Identification of MK-8133: An orexin-2 selective receptor antagonist with favorable development properties
  作者：Scott D. Kuduk、Jason W. Skudlarek、Christina N. DiMarco、Joseph G. Bruno、Mark H. Pausch、Julie A. O’Brien、Tamara D. Cabalu、Joanne Stevens、Joseph Brunner、Pamela L. Tannenbaum、Susan L. Garson、Alan T. Savitz、Charles M. Harrell、Anthony L. Gotter、Christopher J. Winrow、John J. Renger、Paul J. Coleman

  DOI：10.1016/j.bmcl.2015.04.066

  日期：2015.6

  Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were selective for the OX2R subtype. Judicious selection of the substituents on the pyridine ring and benzamide groups led to 6b; which was highly potent, OX2R selective, and exhibited excellent development properties. (C) 2015 Elsevier Ltd. All rights reserved.
• USE OF OX1R ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASES
  申请人：INSERM (Institut National de la Santé et de la Recherche Médicale)

  公开号：EP3223803A1

  公开（公告）日：2017-10-04
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF CANCER
  申请人：UNIVERSITÉ PARIS DIDEROT - PARIS 7

  公开号：US20180296549A1

  公开（公告）日：2018-10-18

  The present invention relates to methods and pharmaceutical compositions for the treatment of cancer. More particularly, the present invention relates to a method of treating cancer in subject in need thereof comprising administering the subject with a therapeutically effective amount of at least one OX1R antagonist.
• METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF AUTOIMMUNE INFLAMMATORY
  申请人：INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCJAE MÉDICALE

  公开号：US20190151304A1

  公开（公告）日：2019-05-23

  The present invention relates to methods and pharmaceutical compositions for the treatment of autoimmune inflammatory diseases. The inventors showed that orexin receptor antagonists have anti-inflammatory properties. Indeed, these compounds are antagonist for OX1R-mediated calcium mobilization but a full agonist for OX1R-mediated mitochondrial apoptosis, which is the mechanism involved in the improvement of resolution of inflammation observed in the models of colitis, multiple sclerosis and pancreatitis. In particular, the present invention relates to a method of treating an autoimmune inflammatory disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of at least one OX1R antagonist.