3-(benzyloxy)-5-ethynylpyridine | 1404372-70-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(benzyloxy)-5-ethynylpyridine
• 英文别名: 3-(Benzyloxy)-5-ethynylpyridine；3-ethynyl-5-phenylmethoxypyridine
• CAS: 1404372-70-8
• 化学式: C₁₄H₁₁NO
• 分子量: 209.247
• InChiKey: CPFLUTFMFPCJNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-5-ethynylpyridine 在 三丁基膦 、 palladium 10% on activated carbon 、 氢气 、 异氰酸苯酯 、 三乙胺 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.75h， 生成 C₁₉H₂₅N₃O₄
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm301177j
• 作为产物：
  描述：

  3-苯甲氧基-5-溴吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 3-(benzyloxy)-5-ethynylpyridine
  参考文献：
  名称：

  高效和选择性α4β2-烟碱乙酰胆碱受体（nAChR）部分激动剂的新型杂种的合成和生物学评估

  摘要：

  我们先前曾报道过环丙基吡啶和异恶唑基吡啶醚支架是通用的构建基块，可用于创建有效的α4β2烟碱型乙酰胆碱受体（nAChR）部分激动剂，其选择性优于α3β4亚型。在我们不断努力开发治疗性烟碱配体的过程中，合理设计，合成和评估了[ 3 H] epibatidine结合竞争研究中的7种新型杂化化合物。将含环丙烷或异恶唑的侧链并入1-（吡啶-3-基）-1,4-二氮杂苯或2-（吡啶-3-基）-2,5-二氮杂双环[2.2]的5位上.1]庚烷导致K i高度有效和选择性的α4β2* nAChR部分激动剂α4β2的值为0.5-51.4 nM，α3β4和α7的亲和力可忽略不计。此外，化合物21，25和30保持的功能简（EC 50和IC 50个的父含氮杂环丁烷化合物的15-50纳米的值）3和4在86 RB +离子通量测定法。体内最有前途的化合物的功效21证实在小鼠SmartCube ®平台和古典强迫游泳测试中，支

  DOI：

  10.1016/j.ejmech.2016.09.016

文献信息

• 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.
• Synthesis and biological evaluation of novel hybrids of highly potent and selective α4β2-Nicotinic acetylcholine receptor (nAChR) partial agonists
  作者：Han-Kun Zhang、J. Brek Eaton、Allison Fedolak、Hendra Gunosewoyo、Oluseye K. Onajole、Dani Brunner、Ronald J. Lukas、Li-Fang Yu、Alan P. Kozikowski

  DOI：10.1016/j.ejmech.2016.09.016

  日期：2016.11

  isoxazolylpyridine ether scaffolds to be versatile building blocks for creating potent α4β2 nicotinic acetylcholine receptor (nAChR) partial agonists with excellent selectivity over the α3β4 subtype. In our continued efforts to develop therapeutic nicotinic ligands, seven novel hybrid compounds were rationally designed, synthesized, and evaluated in [3H]epibatidine binding competition studies. Incorporation

  我们先前曾报道过环丙基吡啶和异恶唑基吡啶醚支架是通用的构建基块，可用于创建有效的α4β2烟碱型乙酰胆碱受体（nAChR）部分激动剂，其选择性优于α3β4亚型。在我们不断努力开发治疗性烟碱配体的过程中，合理设计，合成和评估了[ 3 H] epibatidine结合竞争研究中的7种新型杂化化合物。将含环丙烷或异恶唑的侧链并入1-（吡啶-3-基）-1,4-二氮杂苯或2-（吡啶-3-基）-2,5-二氮杂双环[2.2]的5位上.1]庚烷导致K i高度有效和选择性的α4β2* nAChR部分激动剂α4β2的值为0.5-51.4 nM，α3β4和α7的亲和力可忽略不计。此外，化合物21，25和30保持的功能简（EC 50和IC 50个的父含氮杂环丁烷化合物的15-50纳米的值）3和4在86 RB +离子通量测定法。体内最有前途的化合物的功效21证实在小鼠SmartCube ®平台和古典强迫游泳测试中，支