(S)-tert-butyl 2-((5-((3-fluorophenyl)ethynyl)pyridin-3-yloxy)methyl)azetidine-1-carboxylate | 1434047-78-5

• 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-((3-fluorophenyl)ethynyl)pyridin-3-yloxy)methyl)azetidine-1-carboxylate
• 英文别名: tert-butyl (2S)-2-[[5-[2-(3-fluorophenyl)ethynyl]pyridin-3-yl]oxymethyl]azetidine-1-carboxylate
• CAS: 1434047-78-5
• 化学式: C₂₂H₂₃FN₂O₃
• 分子量: 382.435
• InChiKey: UTOUOVMMDZZIQM-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-((5-((3-fluorophenyl)ethynyl)pyridin-3-yloxy)methyl)azetidine-1-carboxylate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 二氯甲烷 、 甲醇 、 水 为溶剂， 反应 23.0h， 以78%的产率得到(S)-3-(azetidin-2-ylmethoxy)-5-((3-fluorophenyl)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
• 作为产物：
  描述：

  (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-1-carboxylic acid tert-butyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 、 三苯基膦 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 甲苯 为溶剂， 反应 52.0h， 生成 (S)-tert-butyl 2-((5-((3-fluorophenyl)ethynyl)pyridin-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

• 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
• Design, Synthesis and Discovery of Picomolar Selective α4β2 Nicotinic Acetylcholine Receptor Ligands
  作者：Venkata M. Yenugonda、Yingxian Xiao、Edward D. Levin、Amir H. Rezvani、Thao Tran、Nour Al-Muhtasib、Niaz Sahibzada、Teresa Xie、Corinne Wells、Susan Slade、Joshua E. Johnson、Sivanesan Dakshanamurthy、Hye-Sik Kong、York Tomita、Yong Liu、Mikell Paige、Kenneth J. Kellar、Milton L. Brown

  DOI：10.1021/jm4008455

  日期：2013.11.14

  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.