(R)-N-Cbz-2-(o-benzyloxy-p-acetylphenoxyacetyl)pyrrolidine | 1338384-46-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (R)-N-Cbz-2-(o-benzyloxy-p-acetylphenoxyacetyl)pyrrolidine
• CAS: 1338384-46-5
• 化学式: C₂₉H₂₉NO₆
• 分子量: 487.552
• InChiKey: LVPYZNJIBDWVGB-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  36.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  82.14
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3,4-二羟基苯乙酮 在 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 (R)-N-Cbz-2-(o-benzyloxy-p-acetylphenoxyacetyl)pyrrolidine
  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