(1R,2'S)-1-(1'-methyl-2'-pyrrolidinyl)-2-(o-hydroxy-p-bromophenoxy)ethanol | 1338384-74-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (1R,2'S)-1-(1'-methyl-2'-pyrrolidinyl)-2-(o-hydroxy-p-bromophenoxy)ethanol
• 英文别名: 5-bromo-2-[(2R)-2-hydroxy-2-[(2S)-1-methylpyrrolidin-2-yl]ethoxy]phenol
• CAS: 1338384-74-9
• 化学式: C₁₃H₁₈BrNO₃
• 分子量: 316.195
• InChiKey: DJRUQDCSGZOYRU-JQWIXIFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  52.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,2'S)-1-(1'-methyl-2'-pyrrolidinyl)-2-(o-hydroxy-p-bromophenoxy)ethanol 在 偶氮二甲酸二异丙酯 、 三甲基膦 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以69%的产率得到(2S,2'S)-2-(1'-methyl-2'-pyrrolidinyl)-7-bromo-1,4-benzodioxane
  参考文献：
  名称：

  Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2′S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist

  摘要：

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.

  DOI：

  10.1021/jm200937t
• 作为产物：
  描述：

  3-(2-methoxyethoxymethoxy)-4-acetylbromobenzene 在 lithium aluminium tetrahydride 、 间氯过氧苯甲酸 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 (1R,2'S)-1-(1'-methyl-2'-pyrrolidinyl)-2-(o-hydroxy-p-bromophenoxy)ethanol
  参考文献：
  名称：

  Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2′S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist

  摘要：

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.

  DOI：

  10.1021/jm200937t

文献信息

• Unichiral 2-(2′-Pyrrolidinyl)-1,4-benzodioxanes: the 2<i>R</i>,2′<i>S</i> Diastereomer of the <i>N</i>-Methyl-7-hydroxy Analogue Is a Potent α4β2- and α6β2-Nicotinic Acetylcholine Receptor Partial Agonist
  作者：Cristiano Bolchi、Cecilia Gotti、Matteo Binda、Laura Fumagalli、Luca Pucci、Francesco Pistillo、Giulio Vistoli、Ermanno Valoti、Marco Pallavicini

  DOI：10.1021/jm200937t

  日期：2011.11.10

  A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K-i). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles.