(R)-4-benzyl-3-((R)-6,6-diphenyl-1,4-dioxane-2-carbonyl)oxazolidin-2-one | 1357157-81-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-4-benzyl-3-((R)-6,6-diphenyl-1,4-dioxane-2-carbonyl)oxazolidin-2-one
• 英文别名: (4R)-4-benzyl-3-[(2R)-6,6-diphenyl-1,4-dioxane-2-carbonyl]-1,3-oxazolidin-2-one
• CAS: 1357157-81-3
• 化学式: C₂₇H₂₅NO₅
• 分子量: 443.499
• InChiKey: NWLAMSJHEIKWEJ-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-4-benzyl-3-((R)-6,6-diphenyl-1,4-dioxane-2-carbonyl)oxazolidin-2-one 在 锂硼氢 、 水 作用下， 以 乙醚 为溶剂， 以60%的产率得到(S)-(6,6-diphenyl-1,4-dioxan-2-yl)methanol
  参考文献：
  名称：

  1,4-Dioxane, a Suitable Scaffold for the Development of Novel M₃ Muscarinic Receptor Antagonists

  摘要：

  In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M-2/M-3 muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M-3 preferring antagonist (+/-)-17, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects.

  DOI：

  10.1021/jm2013216
• 作为产物：
  描述：

  6,6-diphenyl-1,4-dioxane-2-carboxylic acid 在 正丁基锂 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.75h， 生成 (R)-4-benzyl-3-((R)-6,6-diphenyl-1,4-dioxane-2-carbonyl)oxazolidin-2-one
  参考文献：
  名称：

  1,4-Dioxane, a Suitable Scaffold for the Development of Novel M₃ Muscarinic Receptor Antagonists

  摘要：

  In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M-2/M-3 muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M-3 preferring antagonist (+/-)-17, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects.

  DOI：

  10.1021/jm2013216

文献信息

• Novel muscarinic acetylcholine receptor hybrid ligands embedding quinuclidine and 1,4-dioxane fragments
  作者：Fabio Del Bello、Alessandro Bonifazi、Gianfabio Giorgioni、Riccardo Petrelli、Wilma Quaglia、Angela Altomare、Aurelia Falcicchio、Rosanna Matucci、Giulio Vistoli、Alessandro Piergentili

  DOI：10.1016/j.ejmech.2017.06.004

  日期：2017.9

  To obtain novel muscarinic acetylcholine receptor (mAChR) antagonists, the enantiomers of the hybrid compounds 3-5, in which the quinuclidin-3-yloxy fragment of solifenacin and the 6,6-diphenyl-1,4dioxane-2-yl moiety of 2 linked by an ester or ether spacer were embedded in the same chemical entity, were prepared and evaluated for their affinity at the five mAChR subtypes (M-1-M-5). Stereochemistry and the nature of the linker between the quinuclidine moiety and the 1,4-dioxane nucleus play an important role on the affinities of the compounds. The presence of an ether bridge confers higher affinities for all mAChR subtypes to the ligand. Interestingly, the ether enantiomer (R,S)-5 shows the highest affinity at all mAChR subtypes with K-p(i) values similar to that of solifenacin at M-3 and higher at the other subtypes. Unlike solifenacin, it shows a preference for M-1 mAChR subtype with respect to the other subtypes. This compound, lacking a permanent positive charge on the nitrogen atom, can be a useful tool for the pharmacological study of mAChRs in the central nervous system. (C) 2017 Elsevier Masson SAS. All rights reserved.
• 1,4-Dioxane, a Suitable Scaffold for the Development of Novel M₃ Muscarinic Receptor Antagonists
  作者：Fabio Del Bello、Elisabetta Barocelli、Simona Bertoni、Alessandro Bonifazi、Mercedes Camalli、Gaetano Campi、Mario Giannella、Rosanna Matucci、Marta Nesi、Maria Pigini、Wilma Quaglia、Alessandro Piergentili

  DOI：10.1021/jm2013216

  日期：2012.2.23

  In this study the modulation of the pharmacological profile from agonist to antagonist was successfully obtained by replacing the methyl group in position 6 of the 1,4-dioxane scaffold of the potent M-2/M-3 muscarinic agonist 1 with bulkier groups. In particular, the 6,6-diphenyl substitution provided the potent M-3 preferring antagonist (+/-)-17, which in in vivo study proved to be effective in reducing the volume-induced contractions of rat urinary bladder and was devoid of cardiovascular effects.