2(S)-[(5-ethynylpyridin-3-yloxy)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester | 1222139-62-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 2(S)-[(5-ethynylpyridin-3-yloxy)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: 3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-ethynylpyridine；tert-butyl (2S)-2-[(5-ethynylpyridin-3-yl)oxymethyl]pyrrolidine-1-carboxylate
• CAS: 1222139-62-9
• 化学式: C₁₇H₂₂N₂O₃
• 分子量: 302.373
• InChiKey: QTLWPGXHHVKSMP-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2(S)-[(5-ethynylpyridin-3-yloxy)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 异氰酸苯酯 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 正己烷 、 乙酸乙酯 、 苯 为溶剂， 反应 60.0h， 生成 [5-[5-[(2(S)-pyrrolidinyl)methoxy]-3-pyridyl]-3-isoxazolyl]methanol hydrochloride
  参考文献：
  名称：

  NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF

  摘要：

  该发明涉及吡啶基烟碱乙酰胆碱受体配体，包含有效量吡啶基烟碱乙酰胆碱受体配体的组合物，以及治疗或预防某种疾病的方法，如抑郁症和尼古丁依赖症，包括向需要的动物施用有效量吡啶基烟碱乙酰胆碱受体配体。

  公开号：

  US20130184313A1
• 作为产物：
  描述：

  3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[(trimethylsilyl)ethynyl]pyridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以98%的产率得到2(S)-[(5-ethynylpyridin-3-yloxy)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  [EN] NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
  [FR] LIGANDS DES RÉCEPTEURS CHOLINERGIQUES NICOTINIQUES ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2010045212A3

文献信息

• Nicotinic acetylcholine receptor ligands and the uses thereof
  申请人：Chandrasekhar Jayaraman

  公开号：US08445684B2

  公开（公告）日：2013-05-21

  The invention relates to pyridinyl nicotinic acetylcholine receptor ligands, compositions comprising an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand and methods to treat or prevent a condition, such as depression and nicotine dependence, comprising administering to an animal in need thereof an effective amount of a pyridinyl nicotinic acetylcholine receptor ligand.

  本发明涉及吡啶基烟碱乙酰胆碱受体配体，包括有效量的吡啶基烟碱乙酰胆碱受体配体的组合物，以及用于治疗或预防诸如抑郁症和尼古丁依赖等疾病的方法，包括向需要治疗的动物中投与有效量的吡啶基烟碱乙酰胆碱受体配体。
• Discovery of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists Containing an Isoxazolylpyridine Ether Scaffold that Demonstrate Antidepressant-like Activity. Part II
  作者：Li-Fang Yu、J. Brek Eaton、Allison Fedolak、Han-Kun Zhang、Taleen Hanania、Dani Brunner、Ronald J. Lukas、Alan P. Kozikowski

  DOI：10.1021/jm301177j

  日期：2012.11.26

  In our continued efforts to develop alpha 4 beta 2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certam isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [H-3]epibatidine binding studies together with functional assays based on Rb-86(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.
• US8445684B2
  申请人：——

  公开号：US8445684B2

  公开（公告）日：2013-05-21