3-[(2-methoxyethoxy)methoxy]pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-[(2-methoxyethoxy)methoxy]pyridine
• 英文别名: 3-(2-methoxyethoxymethoxy)pyridine
• 化学式: C₉H₁₃NO₃
• 分子量: 183.207
• InChiKey: YRVXXSLEFQYAQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(2-methoxyethoxy)methoxy]pyridine 在 叔丁基锂 、 六氯乙烷 作用下， 以 乙醚 、 正戊烷 为溶剂， 反应 2.0h， 以90%的产率得到4-chloro-3-[(2-methoxyethoxy)methoxy]pyridine
  参考文献：
  名称：

  From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at α4β2 nicotinic acetylcholine receptor

  摘要：

  Each of the four aromatic -CH= of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as alpha 4 beta 2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes and compared to their common carbaisostere. It turned out that such isosteric substitutions are highly detrimental, but with the important exception of the S,R stereoisomer of the pyrrolidinyl-pyridodioxane with the pyridine nitrogen adjacent to the dioxane and seven atoms distant from the pyrrolidine nitrogen. Indeed, this stereo/regioisomer not only maintained the alpha 4 beta 2 affinity of [(S,R)-6], but also greatly improved in selectivity over the alpha 3 beta 4 and alpha 7 subtypes and, most importantly, exhibited a highly selective alpha 4 beta 2 partial agonism. The finding that [(S,R)-6] is, instead, an unselective alpha 4 beta 2 antagonist indicates that the benzodioxane substructure confers affinity for the alpha 4 beta 2 nAChR binding site, but activation of this receptor subtype needs benzodioxane functionalization under strict steric requirements, such as the previously reported 7-OH substitution or the present isosteric modification. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.10.048
• 作为产物：
  描述：

  3-羟基吡啶 、 2-甲氧基乙氧基甲基氯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.67h， 以38%的产率得到3-[(2-methoxyethoxy)methoxy]pyridine
  参考文献：
  名称：

  From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at α4β2 nicotinic acetylcholine receptor

  摘要：

  Each of the four aromatic -CH= of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as alpha 4 beta 2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes and compared to their common carbaisostere. It turned out that such isosteric substitutions are highly detrimental, but with the important exception of the S,R stereoisomer of the pyrrolidinyl-pyridodioxane with the pyridine nitrogen adjacent to the dioxane and seven atoms distant from the pyrrolidine nitrogen. Indeed, this stereo/regioisomer not only maintained the alpha 4 beta 2 affinity of [(S,R)-6], but also greatly improved in selectivity over the alpha 3 beta 4 and alpha 7 subtypes and, most importantly, exhibited a highly selective alpha 4 beta 2 partial agonism. The finding that [(S,R)-6] is, instead, an unselective alpha 4 beta 2 antagonist indicates that the benzodioxane substructure confers affinity for the alpha 4 beta 2 nAChR binding site, but activation of this receptor subtype needs benzodioxane functionalization under strict steric requirements, such as the previously reported 7-OH substitution or the present isosteric modification. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.10.048