(2S,2'S)-2-(1'-methyl-2'-pyrrolidinyl)-7-phenyl-1,4-benzodioxane | 1338385-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (2S,2'S)-2-(1'-methyl-2'-pyrrolidinyl)-7-phenyl-1,4-benzodioxane
• 英文别名: (2S)-1-methyl-2-[(3S)-6-phenyl-2,3-dihydro-1,4-benzodioxin-3-yl]pyrrolidine
• CAS: 1338385-05-9
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: HDBQBBNRLQCWIT-QFBILLFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-hydroxy-4-phenyl-acetophenone 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 间氯过氧苯甲酸 、 sodium hydroxide 、 三甲基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 99.17h， 生成 (2S,2'S)-2-(1'-methyl-2'-pyrrolidinyl)-7-phenyl-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