5-(iodomethyl)-2,2-diphenyl-1,4-dioxane | 1071507-21-5

• 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: 5-(iodomethyl)-2,2-diphenyl-1,4-dioxane
• CAS: 1071507-21-5
• 化学式: C₁₇H₁₇IO₂
• 分子量: 380.225
• InChiKey: QDQQRCHVQHYGJD-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：

  5-(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， 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)-2,2-diphenylethanol 在 mercury(II) diacetate 、 溶剂黄146 、 potassium iodide 、 碘 作用下， 以 水 、 氯仿 为溶剂， 以47%的产率得到5-(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

• Novel Potent Muscarinic Receptor Antagonists: Investigation on the Nature of Lipophilic Substituents in the 5- and/or 6-Positions of the 1,4-Dioxane Nucleus
  作者：Fabio Del Bello、Alessandro Bonifazi、Gianfabio Giorgioni、Alessandro Piergentili、Maria Giovanna Sabbieti、Dimitrios Agas、Marzia Dell’Aera、Rosanna Matucci、Marcin Górecki、Gennaro Pescitelli、Giulio Vistoli、Wilma Quaglia

  DOI：10.1021/acs.jmedchem.9b02100

  日期：2020.6.11

  A series of novel 1,4-dioxane analogues of the muscarinic acetylcholine receptor (mAChR) antagonist 2 was synthesized and studied for their affinity at M1–M5 mAChRs. The 6-cyclohexyl-6-phenyl derivative 3b, with a cis configuration between the CH2N+(CH3)3 chain in the 2-position and the cyclohexyl moiety in the 6-position, showed pKi values for mAChRs higher than those of 2 and a selectivity profile

  合成了毒蕈碱乙酰胆碱受体（mAChR）拮抗剂2的一系列新型1,4-二恶烷类似物，并研究了它们在M 1 –M 5 mAChRs上的亲和力。在2位的CH 2 N +（CH 3）3链与6位的环己基部分之间具有顺式构型的6-环己基-6-苯基衍生物3b显示出较高的mAChRs p K i值比2的选择性要好，并且选择性分布类似于临床批准的奥昔布宁药物。3b对映体的研究相应的叔胺33b表明，这些丁香体分别为（2 S，6 S）-（-）- 3b和（2 S，6 S）-（-）- 33b。在M 3 mAChR解析的结构上的对接模拟使实验观察合理化。季铵盐功能可防止血脑屏障的穿越，而较高的M 3 / M 2选择性可能会限制心血管副作用，因此3b成为设计可用于外周血的新型拮抗剂的有价值的起点M 3的疾病 受体参与。
• 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.
• Novel Potent <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor Antagonists or σ₁ Receptor Ligands Based on Properly Substituted 1,4-Dioxane Ring
  作者：Alessandro Bonifazi、Fabio Del Bello、Valerio Mammoli、Alessandro Piergentili、Riccardo Petrelli、Cristina Cimarelli、Maura Pellei、Dirk Schepmann、Bernhard Wünsch、Elisabetta Barocelli、Simona Bertoni、Lisa Flammini、Consuelo Amantini、Massimo Nabissi、Giorgio Santoni、Giulio Vistoli、Wilma Quaglia

  DOI：10.1021/acs.jmedchem.5b01214

  日期：2015.11.12

  Two series of 1,4-dioxanes (4–11 and 12–19) were rationally designed and prepared to interact either with the phencyclidine (PCP) binding site of the N-methyl-d-aspartate (NMDA) receptor or with σ1 receptors, respectively. The biological profiles of the novel compounds were assessed using radioligand binding assays, and the compounds with the highest affinities were investigated for their functional

  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。