6-(iodomethyl)-2,2-diphenyl-1,4-dioxane | 1187311-43-8

• 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-(iodomethyl)-2,2-diphenyl-1,4-dioxane
• CAS: 1187311-43-8
• 化学式: C₁₇H₁₇IO₂
• 分子量: 380.225
• InChiKey: MQWCCORVSFZKHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(iodomethyl)-2,2-diphenyl-1,4-dioxane 在 lithium aluminium tetrahydride 、 sodium iodide 作用下， 以 四氢呋喃 、 二甲基亚砜 、 苯 为溶剂， 反应 36.0h， 生成
  参考文献：
  名称：

  新的有效Ñ -甲基d天冬氨酸（NMDA）受体拮抗剂或σ 1受体配体基于上适当取代的1,4-二恶烷环

  摘要：

  两个系列的1,4-二恶烷（4 - 11和12 - 19）的合理设计和制备与苯环利定（PCP）的结合位点或者相互作用Ñ甲基d天冬氨酸（NMDA）受体或与σ 1受体。使用放射性配体结合测定法评估了新化合物的生物学特性，并研究了具有最高亲和力的化合物的功能活性。的结果与可用的药效模型线，并强调的是，1,4-二恶烷支架是与NMDA受体或高亲和力σ有效的拮抗剂活性相容1受体。分别在6位带有环己基和苯环或两个苯环的伯胺6b和7是NMDA受体上最有力的非竞争性拮抗剂，其IC 50值类似于解离性麻醉药（S）-（+ ）-氯胺酮。与在位置2中的苄基氨基甲基部分相关联，如在5,5-二苯基取代18，青睐具有σ相互作用1受体。

  DOI：

  10.1021/acs.jmedchem.5b01214
• 作为产物：
  描述：

  2-(allyloxy)-1,1-diphenylethanol 在 mercury(II) diacetate 、 溶剂黄146 、 potassium iodide 、 碘 作用下， 以 水 、 氯仿 为溶剂， 以28%的产率得到6-(iodomethyl)-2,2-diphenyl-1,4-dioxane
  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
• Multitarget 1,4-Dioxane Compounds Combining Favorable D₂-like and 5-HT_1A Receptor Interactions with Potential for the Treatment of Parkinson’s Disease or Schizophrenia
  作者：Fabio Del Bello、Dario Ambrosini、Alessandro Bonifazi、Amy H. Newman、Thomas M. Keck、Mario Giannella、Gianfabio Giorgioni、Alessandro Piergentili、Loredana Cappellacci、Antonio Cilia、Silvia Franchini、Wilma Quaglia

  DOI：10.1021/acschemneuro.8b00677

  日期：2019.5.15

  2-methoxy derivative 3 showed a multitarget combination of 5-HT1A/D4 agonism and D2/D3/5-HT2A antagonism, which may be a favorable profile for the treatment of schizophrenia. Interestingly, the 3-hydroxy derivative 8 behaved as a partial agonist at D2 and as a potent full agonist at D3 and D4 subtypes. In addition to its potent 5-HT1A receptor agonism, such a dopaminergic profile makes 8 a potential multitarget

  N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-phenoxyethan-1-amine 骨架苯氧基部分不同位置的甲氧基和羟基取代对亲和力的影响评估了 D2 样、5-HT1A 和 α1-肾上腺素能受体亚型的活性。发现了具有多巴胺能和血清素能谱的合适组合的多目标化合物。特别是，2-甲氧基衍生物 3 表现出 5-HT1A/D4 激动和 D2/D3/5-HT2A 拮抗的多靶点组合，这可能是治疗精神分裂症的有利特征。有趣的是，3-羟基衍生物 8 在 D2 中充当部分激动剂，在 D3 和 D4 亚型中充当有效的完全激动剂。除了其有效的 5-HT1A 受体激动作用外，这种多巴胺能谱使 8 成为治疗帕金森症的潜在多靶点化合物 s 疾病 (PD)。事实上，5-HT1A 受体的激活可能有助于减少与多巴胺能刺激相关的运动障碍副作用。
• 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.