ZW-87 | 820231-75-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ZW-87
• 英文别名: 3-ethynyl-5-[(1-methyl-2(S)-pyrrolidinyl)methoxy]pyridine；5-(1-ethynyl)-3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine；3-[(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-ethynylpyridine；3-ethynyl-5-((S)-1-methylpyrrolidin-2-ylmethoxy)pyridine；3-Ethynyl-5-{[(2S)-1-methyl-2-pyrrolidinyl]methoxy}pyridine；3-ethynyl-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine
• CAS: 820231-75-2
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: ZDTSCWZPUHXKPB-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  25.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ZW-87 、 4-硝基丁酸甲酯 在 异氰酸苯酯 、 三乙胺 作用下， 以 苯 为溶剂， 反应 24.0h， 以98%的产率得到3-[5-[5-[[1-methyl-2(S)-pyrrolidinyl]methoxy]-3-pyridyl]-3-isoxazolyl]propionic acid methyl ester
  参考文献：
  名称：

  [EN] NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS AND THE USES THEREOF
  [FR] LIGANDS DES RÉCEPTEURS CHOLINERGIQUES NICOTINIQUES ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2010045212A3
• 作为产物：
  描述：

  N-甲基-L-脯氨醇 在 palladium on activated charcoal copper(l) iodide 、 sodium hydride 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 123.0h， 生成 ZW-87
  参考文献：
  名称：

  Novel Pyridyl Ring C5 Substituted Analogues of Epibatidine and 3-(1-Methyl-2(S)- pyrrolidinylmethoxy)pyridine (A-84543) as Highly Selective Agents for Neuronal Nicotinic Acetylcholine Receptors Containing β2 Subunits

  摘要：

  Introduction of a hydrophobic or hydrogen-bonding alkynyl group into the C5 position of the pyridyl ring of epibatidine and A-84543 significantly increased the selectivity for neuronal nicotinic acetylcholine receptors (nAChRs) containing beta 2 subunits over nACbRs containing beta 4 subunits (K-i ratio up to 92000-fold). Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes.

  DOI：

  10.1021/jm0492406

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。
• Ligands for Nicotinic Acetylcholine Receptors, and Methods of Making and Using Them
  申请人：Kozikowski Alan P.

  公开号：US20080132486A1

  公开（公告）日：2008-06-05

  One aspect of the present invention relates to heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. A second aspect of the invention relates to the use of a compound of the invention for modulation of a mammalian nicotinic acetylcholine receptor. The present invention also relates to the use of a compound of the invention for treating a mammal suffering from Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism or trichtillomania.

  本发明的一个方面涉及杂环化合物，其是乙酰胆碱受体的配体。本发明的第二个方面涉及使用本发明的化合物来调节哺乳动物的乙酰胆碱受体。本发明还涉及使用本发明的化合物来治疗患有阿尔茨海默病、帕金森病、运动障碍、抽动症、精神分裂症、注意力缺陷障碍、焦虑、疼痛、抑郁症、强迫症、化学物质滥用、酗酒、记忆力障碍、假性痴呆、甘瑟综合征、偏头痛疼痛、贪食症、肥胖症、月经前综合征或黄体酮期后综合征、烟草滥用、创伤后应激障碍、社交恐惧症、慢性疲劳综合征、早泄、勃起障碍、厌食症、睡眠障碍、自闭症、哑症或拔毛癖的哺乳动物。
• Ligands for nicotinic acetylcholine receptors, and methods of making and using them
  申请人：Georgetown University

  公开号：US08030300B2

  公开（公告）日：2011-10-04

  One aspect of the present invention relates to heterocyclic compounds that are ligands for nicotinic acetylcholine receptors. A second aspect of the invention relates to the use of a compound of the invention for modulation of a mammalian nicotinic acetylcholine receptor. The present invention also relates to the use of a compound of the invention for treating a mammal suffering from Alzheimer's disease, Parkinson's disease, dyskinesias, Tourette's syndrome, schizophrenia, attention deficit disorder, anxiety, pain, depression, obsessive compulsive disorder, chemical substance abuse, alcoholism, memory deficit, pseudodementia, Ganser's syndrome, migraine pain, bulimia, obesity, premenstrual syndrome or late luteal phase syndrome, tobacco abuse, post-traumatic syndrome, social phobia, chronic fatigue syndrome, premature ejaculation, erectile difficulty, anorexia nervosa, disorders of sleep, autism, mutism or trichtillomania.

  本发明的一个方面涉及杂环化合物，其是乙酰胆碱受体的配体。本发明的第二个方面涉及使用本发明的化合物来调节哺乳动物的乙酰胆碱受体。本发明还涉及使用本发明的化合物来治疗患有阿尔茨海默病、帕金森病、运动障碍、抽动症、精神分裂症、注意力缺陷障碍、焦虑、疼痛、抑郁、强迫症、化学物质滥用、酗酒、记忆力缺失、假性痴呆、甘瑟综合征、偏头痛、贪食症、肥胖症、经前期综合征或晚期黄体期综合征、烟草滥用、创伤后综合征、社交恐惧症、慢性疲劳综合征、早泄、勃起障碍、厌食症、睡眠障碍、自闭症、缄默症或拔毛癖的哺乳动物。
• [EN] LIGANDS FOR NICOTINIC ACETYLCHOLINE RECEPTORS, AND METHODS OF MAKING AND USING THEM<br/>[FR] LIGANDS POUR LES RECEPTEURS DE L'ACETYLCHOLINE NICOTINIQUE, ET PROCEDES DE PRODUCTION ET D'UTILISATION DE CES LIGANDS
  申请人：UNIV GEORGETOWN

  公开号：WO2005000806A3

  公开（公告）日：2005-03-24
• 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.