N,N-dimethyl-2-{[5-(pyrrolidin-1-yl)pyridin-3-yl]oxy}ethanamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N,N-dimethyl-2-{[5-(pyrrolidin-1-yl)pyridin-3-yl]oxy}ethanamine
• 英文别名: N,N-dimethyl-2-(5-pyrrolidin-1-ylpyridin-3-yl)oxyethanamine
• 化学式: C₁₃H₂₁N₃O
• 分子量: 235.329
• InChiKey: YARLOACCXFVQRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  28.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  四氢吡咯 、 2-[(5-溴-3-吡啶基)氧基]-N,N-二甲基乙胺 在 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 、 叔丁醇 为溶剂， 反应 80.0h， 以86%的产率得到N,N-dimethyl-2-{[5-(pyrrolidin-1-yl)pyridin-3-yl]oxy}ethanamine
  参考文献：
  名称：

  The twin drug approach for novel nicotinic acetylcholine receptor ligands

  摘要：

  The association of two pharmacophoric entities generates so-called 'twin drugs' or dimer derivatives. We applied this approach for the design of a small compound library for the interaction with alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs). In this compound series, the nAChR ligand N, N-dimethyl-2-(pyridin-3-yloxy) ethan-1-amine 9 served as one pharmacological entity and it was initially kept constant as one part of the 'twin' compound. 'Twin' compounds with identical or non-identical entities using the 'no linker mode' or 'overlap' mode were synthesized and evaluated for their nAChR affinities. Compound 17a showed the highest affinity for the alpha 4 beta 2* nAChR subtype (K-i = 0.188 nM) and its (di)fluoro analogs could retain nanomolar affinities, when replacing pyridine as the hydrogen bond acceptor system by mono-or difluoro-phenyls. The 'twin drug' approach proved to provide compounds with high affinity and subtype selectivity for alpha 4 beta 2* nAChRs. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.034

文献信息

• The twin drug approach for novel nicotinic acetylcholine receptor ligands
  作者：Isabelle Tomassoli、Daniela Gündisch

  DOI：10.1016/j.bmc.2015.06.034

  日期：2015.8

  The association of two pharmacophoric entities generates so-called 'twin drugs' or dimer derivatives. We applied this approach for the design of a small compound library for the interaction with alpha 4 beta 2* nicotinic acetylcholine receptors (nAChRs). In this compound series, the nAChR ligand N, N-dimethyl-2-(pyridin-3-yloxy) ethan-1-amine 9 served as one pharmacological entity and it was initially kept constant as one part of the 'twin' compound. 'Twin' compounds with identical or non-identical entities using the 'no linker mode' or 'overlap' mode were synthesized and evaluated for their nAChR affinities. Compound 17a showed the highest affinity for the alpha 4 beta 2* nAChR subtype (K-i = 0.188 nM) and its (di)fluoro analogs could retain nanomolar affinities, when replacing pyridine as the hydrogen bond acceptor system by mono-or difluoro-phenyls. The 'twin drug' approach proved to provide compounds with high affinity and subtype selectivity for alpha 4 beta 2* nAChRs. (C) 2015 Elsevier Ltd. All rights reserved.