(6,6-diphenyl-1,4-dioxan-2-yl)methanol | 1071506-62-1

• 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: (6,6-diphenyl-1,4-dioxan-2-yl)methanol
• CAS: 1071506-62-1
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: BYJIFKDOSSFUIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (6,6-diphenyl-1,4-dioxan-2-yl)methanol 在 氢氧化钾 、 potassium permanganate 作用下， 以 水 为溶剂， 反应 18.0h， 以52%的产率得到6,6-diphenyl-1,4-dioxane-2-carboxylic acid
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm800461k
• 作为产物：
  描述：

  2-(oxiran-2-ylmethoxy)-1,1-diphenylethanol 在 D(+)-10-樟脑磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 以60%的产率得到(6,6-diphenyl-1,4-dioxan-2-yl)methanol
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm800461k

文献信息

• The replacement of the 2-methoxy substituent of N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-(2-methoxyphenoxy)ethan-1-amine improves the selectivity for 5-HT1A receptor over α1-adrenoceptor and D2-like receptor subtypes
  作者：Fabio Del Bello、Alessandro Bonifazi、Mario Giannella、Gianfabio Giorgioni、Alessandro Piergentili、Riccardo Petrelli、Carlo Cifani、Maria Vittoria Micioni Di Bonaventura、Thomas M. Keck、Angelica Mazzolari、Giulio Vistoli、Antonio Cilia、Elena Poggesi、Rosanna Matucci、Wilma Quaglia

  DOI：10.1016/j.ejmech.2016.09.026

  日期：2017.1

  interactions of the reported ligands, docking studies, using 5-HT1A and α1d-AR models generated by homology techniques, and a retrospective computational study were performed. The results highlighted that proper substituents in position 2 of the phenoxy moiety of 3 selectively address the ligands toward 5-HT1A receptor with respect to α1-ARs and D2-like receptor subtypes. Methoxymethylenoxy derivative

  ñ - （（6,6-二苯基-1,4-二恶烷-2-基）甲基）-2-（2-甲氧基苯氧基）乙烷-1-胺（3）是一种有效的5-HT 1A受体和α 1D -肾上腺素能受体（α1d -AR）配体。类似物5-10被合理地设计和制备，以评估是否在取代基中的电子和/或亲脂性的邻位其苯氧基部分的上施加的亲和/活性的任何有利的作用位置在5-HT 1A受体和改进对α选择性1 - AR。为了使实验观察合理化并获得有关已报道配体的受体-配体相互作用的信息，需要使用5-HT 1A和α进行对接研究通过同源技术生成1d -AR模型，并进行回顾性计算研究。结果强调了的苯氧基部分的2位上，适当的取代基3选择性地寻址朝向5-HT的配位体1A受体相对于α 1个-ARs和d 2 -样受体亚型。甲氧基甲基烯氧基衍生物9表现出最佳的5-HT 1A选择性和对5-HT 1A受体的最高效能，表现为部分激动剂。最后9在小鼠的明/暗探索测试中进行