(2-(5-(Benzyloxy)pyridin-3-YL)cyclopropyl)methanol | 2089650-75-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-(5-(Benzyloxy)pyridin-3-YL)cyclopropyl)methanol
• 英文别名: [2-(5-phenylmethoxypyridin-3-yl)cyclopropyl]methanol
• CAS: 2089650-75-7
• 化学式: C₁₆H₁₇NO₂
• 分子量: 255.316
• InChiKey: XNAQOBNQFXHBBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  42.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-(5-(Benzyloxy)pyridin-3-YL)cyclopropyl)methanol 在 硼烷四氢呋喃络合物 、 草酰氯 、 sodium hexamethyldisilazane 、 二甲基亚砜 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 环己烷 为溶剂， 反应 7.33h， 生成 2-[(1R,2S)-2-[5-(benzyloxy)pyridin-3-yl]cyclopropyl]-ethanol
  参考文献：
  名称：

  Chemistry and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile

  摘要：

  Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing alpha 4 beta 2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at alpha 4 beta 2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other alpha 4 beta 2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.

  DOI：

  10.1021/jm201157c
• 作为产物：
  描述：

  3-苯甲氧基-5-溴吡啶 在 4-二甲氨基吡啶 、 苯基脲 、 palladium diacetate 、 sodium hydride 、 二异丁基氢化铝 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 (2-(5-(Benzyloxy)pyridin-3-YL)cyclopropyl)methanol
  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

• NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
  申请人：Chandrasekhar Jayaraman

  公开号：US20130184313A1

  公开（公告）日：2013-07-18

  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.

  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。
• [EN] NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF<br/>[FR] LIGANDS DES RÉCEPTEURS CHOLINERGIQUES NICOTINIQUES ET LEURS UTILISATIONS
  申请人：PSYCHOGENICS INC

  公开号：WO2010045212A3

  公开（公告）日：2010-07-29
• US8445684B2
  申请人：——

  公开号：US8445684B2

  公开（公告）日：2013-05-21
• Chemistry and Behavioral Studies Identify Chiral Cyclopropanes as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists Exhibiting an Antidepressant Profile
  作者：Hankun Zhang、Werner Tückmantel、J. Brek Eaton、Po-wai Yuen、Li-Fang Yu、Krishna Mohan Bajjuri、Allison Fedolak、Daguang Wang、Afshin Ghavami、Barbara Caldarone、Neil E. Paterson、David A. Lowe、Daniela Brunner、Ronald J. Lukas、Alan P. Kozikowski

  DOI：10.1021/jm201157c

  日期：2012.1.26

  Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing alpha 4 beta 2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at alpha 4 beta 2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other alpha 4 beta 2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.
• 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