5-(6-iodo-1-hexynyl)-3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine | 820231-98-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(6-iodo-1-hexynyl)-3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine
• 英文别名: 3-(6-iodohex-1-ynyl)-5-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]pyridine
• CAS: 820231-98-9
• 化学式: C₁₇H₂₃IN₂O
• 分子量: 398.287
• InChiKey: JUYVLWANRQTJCC-INIZCTEOSA-N

物化性质

• 沸点：
  469.1±40.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 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：

  5-(6-iodo-1-hexynyl)-3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine 在 silver fluoride 作用下， 以 乙腈 为溶剂， 反应 10.0h， 以57%的产率得到ZW-110
  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
• 作为产物：
  描述：

  N-甲基-L-脯氨醇 在 palladium on activated charcoal 咪唑 、 copper(l) iodide 、 碘 、 sodium hydride 、 potassium carbonate 、 三苯基膦 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 125.0h， 生成 5-(6-iodo-1-hexynyl)-3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine
  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

• 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。
• US8030300B2
  申请人：——

  公开号：US8030300B2

  公开（公告）日：2011-10-04
• Novel Pyridyl Ring C5 Substituted Analogues of Epibatidine and 3-(1-Methyl-2(<i>S</i>)- pyrrolidinylmethoxy)pyridine (A-84543) as Highly Selective Agents for Neuronal Nicotinic Acetylcholine Receptors Containing β2 Subunits
  作者：Zhi-Liang Wei、Yingxian Xiao、Hongbin Yuan、Maryna Baydyuk、Pavel A. Petukhov、John L. Musachio、Kenneth J. Kellar、Alan P. Kozikowski

  DOI：10.1021/jm0492406

  日期：2005.3.1

  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.