(S)-3-(azetidin-2-ylmethoxy)-5-((3-fluoro-5-methoxyphenyl)ethynyl)pyridine | 1434047-71-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-3-(azetidin-2-ylmethoxy)-5-((3-fluoro-5-methoxyphenyl)ethynyl)pyridine
• 英文别名: 3-[[(2S)-azetidin-2-yl]methoxy]-5-[2-(3-fluoro-5-methoxyphenyl)ethynyl]pyridine
• CAS: 1434047-71-8
• 化学式: C₁₈H₁₇FN₂O₂
• 分子量: 312.344
• InChiKey: WMCQLMHGBWMGAH-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  43.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  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 39.0h， 生成 (S)-3-(azetidin-2-ylmethoxy)-5-((3-fluoro-5-methoxyphenyl)ethynyl)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

文献信息

• [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。
• PHENYL-SUBSTITUTED NICOTINIC LIGANDS, AND METHODS OF USE THEREOF
  申请人：Georgetown University

  公开号：EP2776423B1

  公开（公告）日：2020-05-06
• Phenyl-Substituted Nicotinic Ligands, and Methods of Use Thereof
  申请人：Georgetown University

  公开号：US20140323461A1

  公开（公告）日：2014-10-30

  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.
• US9346784B2
  申请人：——

  公开号：US9346784B2

  公开（公告）日：2016-05-24
• US9994548B2
  申请人：——

  公开号：US9994548B2

  公开（公告）日：2018-06-12