6,6-diphenyl-1,4-dioxane-2-carboxylic acid | 1071506-70-1

• 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-dioxane-2-carboxylic acid
• CAS: 1071506-70-1
• 化学式: C₁₇H₁₆O₄
• 分子量: 284.312
• InChiKey: CJRYBZGFHPDCSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 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：

  6,6-diphenyl-1,4-dioxane-2-carboxylic acid 在 锂硼氢 、 正丁基锂 、 草酰氯 、 水 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 2.75h， 生成 (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-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

文献信息

• Scaffold Hybridization Strategy Leads to the Discovery of Dopamine D₃ Receptor-Selective or Multitarget Bitopic Ligands Potentially Useful for Central Nervous System Disorders
  作者：Alessandro Bonifazi、Amy H. Newman、Thomas M. Keck、Silvia Gervasoni、Giulio Vistoli、Fabio Del Bello、Gianfabio Giorgioni、Pegi Pavletić、Wilma Quaglia、Alessandro Piergentili

  DOI：10.1021/acschemneuro.1c00368

  日期：2021.10.6

  multitarget behavior has been highlighted for the 5,5-diphenyl-1,4-dioxane and 1,4-benzodioxane derivatives 6 and 9, respectively, which displayed potent D2R antagonism, 5-HT1AR and D4R agonism, as well as potent D3R partial agonism. They also behaved as low-potency 5-HT2AR antagonists and 5-HT2CR partial agonists. Such a profile might be a promising starting point for the discovery of novel antipsychotic agents

  在寻找靶向多巴胺 D 3受体 (D 3 R) 的新型双位化合物时，N -(2,3-二氯苯基)哌嗪核（主要药效团）已与 6,6- 或 5,5-二苯基连接-1,4-二恶烷-2-甲酰胺或 1,4-苯并二恶烷-2-甲酰胺支架（二级药效团）由未取代或 3-F-/3-OH-取代的丁基链构成。这种支架杂交策略导致发现了可能对中枢神经系统疾病有用的有效的 D 3 R 选择性或多靶标配体。特别地，6,6-二苯基-1,4-二恶烷衍生物3显示出D 3R 优先分布，而 5,5-二苯基-1,4-二恶烷和 1,4-苯二恶烷衍生物6和9分别显示出有效的 D 2 R 拮抗作用，5-HT 的多靶点行为1A R 和 D 4 R 激动，以及有效的 D 3 R 部分激动。它们还表现为低效 5-HT 2A R 拮抗剂和 5-HT 2C R 部分激动剂。这样的概况可能是发现新型抗精神病药物的一个有希望的起点。
• 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.
• 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.
• 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.