(2S,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-trityloxy-1,4-benzodioxane | 1338384-71-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2S,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-trityloxy-1,4-benzodioxane
• 英文别名: tert-butyl (2S)-2-[(3S)-6-(trityloxymethyl)-2,3-dihydro-1,4-benzodioxin-3-yl]pyrrolidine-1-carboxylate
• CAS: 1338384-71-6
• 化学式: C₃₇H₃₉NO₅
• 分子量: 577.72
• InChiKey: ACHFTKMEAWZEGF-AFPLUKJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-trityloxy-1,4-benzodioxane 在 盐酸 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 5.0h， 生成 (2S,2'S)-2-(1'-methyl-2'-pyrrolidinyl)-7-hydroxymethyl-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：

  (S)-2-(2-bromoacetyl)pyrrolidine-1-carboxylic acid tert-butyl ester 在 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， -20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 17.17h， 生成 (2S,2'S)-2-(1'-Boc-2'-pyrrolidinyl)-7-trityloxy-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

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.