(S)-tert-butyl 2-((5-ethynylpyridin-3-yloxy)methyl)azetidine-1-carboxylate | 1222139-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: (S)-tert-butyl 2-((5-ethynylpyridin-3-yloxy)methyl)azetidine-1-carboxylate
• 英文别名: 3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-ethynylpyridine；tert-butyl (2S)-2-[(5-ethynylpyridin-3-yl)oxymethyl]azetidine-1-carboxylate
• CAS: 1222139-46-9
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: MMWUDCNLXDIVOI-ZDUSSCGKSA-N

物化性质

• 沸点：
  417.0±30.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  (S)-tert-butyl 2-((5-ethynylpyridin-3-yloxy)methyl)azetidine-1-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 41.0h， 生成 (S)-3-(azetidin-2-ylmethoxy)-5-(phenylethynyl)pyridine
  参考文献：
  名称：

  Design, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands

  摘要：

  Developing novel and selective compounds that desensitize alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for alpha 4 beta 2 nicotinic receptors. The novel compounds have K-i; values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes alpha 4 beta 2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs.

  DOI：

  10.1021/jm4008455
• 作为产物：
  描述：

  tert-butyl (S)-2-(hydroxymethyl)aziridine-1-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 、 三苯基膦 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 为溶剂， 反应 82.0h， 生成 (S)-tert-butyl 2-((5-ethynylpyridin-3-yloxy)methyl)azetidine-1-carboxylate
  参考文献：
  名称：

  Design, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands

  摘要：

  Developing novel and selective compounds that desensitize alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) could provide new effective treatments for nicotine addiction, as well as other disorders. Here we report a new class of nAChR ligands that display high selectivity and picomolar binding affinity for alpha 4 beta 2 nicotinic receptors. The novel compounds have K-i; values in the range of 0.031-0.26 nM and properties that should make them good candidates as drugs acting in the CNS. The selected lead compound 1 (VMY-2-95) binds with high affinity and potently desensitizes alpha 4 beta 2 nAChRs. At a dose of 3 mg/kg, compound 1 significantly reduced rat nicotine self-administration. The overall results support further characterizations of compound 1 and its analogues in preclinical models of nicotine addiction and perhaps other disorders involving nAChRs.

  DOI：

  10.1021/jm4008455

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] PHENYL-SUBSTITUTED NICOTINIC LIGANDS, AND METHODS OF USE THEREOF<br/>[FR] LIGANDS NICOTINIQUES SUBSTITUÉS PAR UN PHÉNYLE, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV GEORGETOWN

  公开号：WO2013071067A1

  公开（公告）日：2013-05-16

  Disclosed are compounds and methods of using them to treat a disorder selected from the group consisting of addiction, pain, obesity, schizophrenia, epilepsy, mania and manic depression, anxiety, Alzheimer's disease, learning deficit, cognition deficit, attention deficit, memory loss, Lewy Body Dementia, Attention Deficit Hyperactivity Disorder (ADHD), Parkinson's disease, Huntington's disease, Tourette's syndrome, amyotrophic lateral sclerosis, inflammation, stroke, spinal cord injury, dyskinesias, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, autism, mutism, trichotillomania, hypothermia, and disorders of sleep.

  本发明涉及化合物及其使用方法，用于治疗以下疾病中的一种或多种：成瘾、疼痛、肥胖、精神分裂症、癫痫、躁狂和躁郁症、焦虑、阿尔茨海默病、学习缺陷、认知缺陷、注意力缺陷、记忆丧失、Lewy体痴呆、注意力缺陷多动障碍（ADHD）、帕金森病、亨廷顿病、抽动症、肌萎缩性侧索硬化、炎症、中风、脊髓损伤、运动障碍、强迫症、化学物质滥用、酗酒、记忆缺失、假性痴呆、甘瑟综合症、偏头痛、贪食症、经前综合症或晚期黄体期综合症、吸烟成瘾、创伤后综合症、社交恐惧症、慢性疲劳综合症、早泄、勃起障碍、厌食症、孤独症、缄默症、拔毛癖、低体温症和睡眠障碍疾病。
• 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 Isoxazole Analogues of Sazetidine-A as Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists for the Treatment of Depression
  作者：Jianhua Liu、Li-Fang Yu、J. Brek Eaton、Barbara Caldarone、Katie Cavino、Christina Ruiz、Matthew Terry、Allison Fedolak、Daguang Wang、Afshin Ghavami、David A. Lowe、Dani Brunner、Ronald J. Lukas、Alan P. Kozikowski

  DOI：10.1021/jm200855b

  日期：2011.10.27

  Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with alpha 4 beta 2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the alpha 4 beta 2 subtype of nAChR over alpha 3 beta 4-nAChRs are partial agonists at the alpha 4 beta 2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline.
• [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