trans-5-phenyl-1,4-dioxane-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: trans-5-phenyl-1,4-dioxane-2-carboxylic acid
• 英文别名: rel-(2R,5R)-5-Phenyl-1,4-dioxane-2-carboxylic acid；(2R,5R)-5-phenyl-1,4-dioxane-2-carboxylic acid
• 化学式: C₁₁H₁₂O₄
• 分子量: 208.214
• InChiKey: NUGDMLWDMRRLCH-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-5-phenyl-1,4-dioxane-2-carboxylic acid 在 硫酸 、 三甲基铝 作用下， 以 甲苯 为溶剂， 反应 9.0h， 生成 (2S,5R)-(-)-2-(5-phenyl-1,4-dioxan-2-yl)-4,5-dihydro-1H-imidazole
  参考文献：
  名称：

  Favourable involvement of α2A-adrenoreceptor antagonism in the I2-imidazoline binding sites-mediated morphine analgesia enhancement

  摘要：

  Aim of the present study was to obtain novel alpha(2)-adrenoreceptor (alpha(2)-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective alpha(2)-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole alpha(2A)-subtype. Moreover, 2 showed an affinity at I-2-imidazoline binding sites (I-2-IBS) comparable to that at alpha(2A)-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of alpha(2A)-AR antagonism in the I-2-IBS-mediated morphine analgesia enhancement. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.016
• 作为产物：
  描述：

  (R)-methyl 2-(allyloxy)-2-phenylacetate 在 potassium permanganate 、 lithium aluminium tetrahydride 、 D(+)-10-樟脑磺酸 、 间氯过氧苯甲酸 、 potassium hydroxide 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 trans-5-phenyl-1,4-dioxane-2-carboxylic acid
  参考文献：
  名称：

  Favourable involvement of α2A-adrenoreceptor antagonism in the I2-imidazoline binding sites-mediated morphine analgesia enhancement

  摘要：

  Aim of the present study was to obtain novel alpha(2)-adrenoreceptor (alpha(2)-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective alpha(2)-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole alpha(2A)-subtype. Moreover, 2 showed an affinity at I-2-imidazoline binding sites (I-2-IBS) comparable to that at alpha(2A)-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of alpha(2A)-AR antagonism in the I-2-IBS-mediated morphine analgesia enhancement. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.016

文献信息

• Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 9. From 1,4-Benzodioxane to 1,4-Dioxane Ring as a Promising Template of Novel α_1D-Adrenoreceptor Antagonists, 5-HT_1A Full Agonists, and Cytotoxic Agents
  作者：Wilma Quaglia、Alessandro Piergentili、Fabio Del Bello、Yogita Farande、Mario Giannella、Maria Pigini、Giovanni Rafaiani、Antonio Carrieri、Consuelo Amantini、Roberta Lucciarini、Giorgio Santoni、Elena Poggesi、Amedeo Leonardi

  DOI：10.1021/jm800461k

  日期：2008.10.23

  Novel 1,4-dioxane compounds structurally related to WB 4101 (1) were prepared in order to investigate the possibility that the quite planar 1,4-benzodioxane template of I might be replaced by the less conformationally constrained 1,4-dioxane ring. The biological profiles of the new compounds were assessed using binding assays at human cloned alpha(1)-adrenoreceptor (alpha(1)-AR) subtypes and 5-HT1A receptors, expressed in Chinese hamster ovary and HeLa cell membranes, respectively, and by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)). Moreover, the cytotoxic effects of the novel compounds were determined in PC-3 prostate cancer cells. The results showed that the properly substituted 1,4-dioxane nucleus proved to be a suitable scaffold for selective alpha(1D)-AR antagonists (compound 14), potential anticancer agents (compound 13), and full 5-HT1A receptor agonists (compound 15). In particular, compound 15 may represent a novel lead in the development of highly potent 5-HT1A receptor full agonists useful as antidepressant and neuroprotective agents.
• Favourable involvement of α2A-adrenoreceptor antagonism in the I2-imidazoline binding sites-mediated morphine analgesia enhancement
  作者：Valerio Mammoli、Alessandro Bonifazi、Fabio Del Bello、Eleonora Diamanti、Mario Giannella、Alan L. Hudson、Laura Mattioli、Marina Perfumi、Alessandro Piergentili、Wilma Quaglia、Federica Titomanlio、Maria Pigini

  DOI：10.1016/j.bmc.2012.02.016

  日期：2012.4

  Aim of the present study was to obtain novel alpha(2)-adrenoreceptor (alpha(2)-AR) antagonists, possibly endowed with subtype-selectivity. Therefore, inspired by the non subtype-selective alpha(2)-AR antagonist idazoxan, we designed 1,4-dioxane derivatives bearing an aromatic area in position 5 or 6 and the imidazoline nucleus in position 2. Among the novel molecules 1-6, compound 2, with a trans stereochemical relationship between 5-phenyl and 2-imidazoline groups, was able to antagonize the sole alpha(2A)-subtype. Moreover, 2 showed an affinity at I-2-imidazoline binding sites (I-2-IBS) comparable to that at alpha(2A)-AR. In in vivo studies 2 strongly increased morphine analgesia. This interesting behaviour appeared to be induced by the favourable involvement of alpha(2A)-AR antagonism in the I-2-IBS-mediated morphine analgesia enhancement. (C) 2012 Elsevier Ltd. All rights reserved.