1-((6-bromohexyl)oxy)-4-(tert-butyl)benzene

• 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: 1-((6-bromohexyl)oxy)-4-(tert-butyl)benzene
• 英文别名: 1-[(6-Bromohexyl)oxy]-4-tert-butylbenzene；1-(6-bromohexoxy)-4-tert-butylbenzene
• 化学式: C₁₆H₂₅BrO
• 分子量: 313.278
• InChiKey: JHRHDTGWGMFEKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3-pyridyl)-2-imidazolidinone 、 1-((6-bromohexyl)oxy)-4-(tert-butyl)benzene 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 以82%的产率得到1-[6-(4-tert-Butyl-phenoxy)-hexyl]-3-pyridin-3-yl-imidazolidin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of Pyridyl Imidazolidinones:  A Novel Class of Potent and Selective Human Enterovirus 71 Inhibitors

  摘要：

  When skeletons of Win compounds were used as templates, computer-assisted drug design led to the identification of a novel series of imidazolidinone derivatives with significant antiviral activity against enterovirus 71(EV 71), the infection of which had resulted in about 80 fatalities during the 1998 epidemic outbreak in Taiwan. In addition to inhibiting all the genotypes (A, B, and C) of EV 71 in the submicromolar to low micromolar range, compounds 1 and 8 were extensively evaluated against a variety of viruses, showing potent activity against coxsackievirus A9 (IC50 = 0.47-0.55 muM) and coxsackievirus A24 (IC50 = 0.47-0.55 muM) as well as moderate activity against enterovirus 68 (IC50 = 2.13 muM) and echovirus 9 (IC50 = 2.6 muM). Our SAR studies revealed that imidazolidinone analogues with an aryl substituent at the para position of the phenoxyl ring, such as compounds 20, 21, 27, 57, 58, and 61, in general exhibited the highest activity against EV 71. Among them, compound 20 and its corresponding hydrochloride salt 57, in terms of potency and selectivity index, appear to be the most promising candidates in this series for further development of anti-EV-71 agents. Preliminary results of the study on the mode of action by a time-course experiment suggest that test compounds 1 and 8 can effectively inhibit the virus replication at the early stages, referring to virus attachment or uncoating. This indicates that the surface protein may be the target for this type of compounds.

  DOI：

  10.1021/jm010536a
• 作为产物：
  描述：

  1,6-二溴己烷 、 4-叔丁基苯酚 在 sodium n-propoxide 作用下， 反应 6.25h， 生成 1-((6-bromohexyl)oxy)-4-(tert-butyl)benzene
  参考文献：
  名称：

  具有4-叔丁基丁基苯氧基支架作为组胺H3受体拮抗剂和单胺氧化酶B抑制剂的双重目标配体。

  摘要：

  双靶配体是治疗帕金森氏病（PD）的有前途的概念。单胺氧化酶B（MAO B）抑制与组胺H3受体（H3R）拮抗作用的组合可能对多巴胺调节产生积极影响。因此，基于1-（3-（4-叔丁基苯氧基）丙基）哌啶（DL76）的结构，设计了一系列的二十七个4-叔丁基苯氧基烷氧基胺作为PD的潜在双靶配体。探索的修饰包括引入不同的环胺和延长烷基链。研究了合成的化合物对人H3R（hH3R）的亲和力和对人MAO B（hMAO B）的抑制活性。大多数化合物显示出良好的hH3R亲和力，Ki值低于400 nM，其中一些显示出对hMAO B的有效抑制活性，IC50值低于50 nM。然而，对两种生物学靶标的最平衡活性为DL76（hH3R：Ki = 38 nM和hMAO B：IC50 = 48 nM）。因此，选择了DL76进行进一步研究，揭示了DL76在HEK293和神经母细胞瘤SH-SY5Y细胞中的无毒性质。但是，在过氧化氢

  DOI：

  10.3390/ijms21103411

文献信息

• Structural modifications and in vitro pharmacological evaluation of 4-pyridyl-piperazine derivatives as an active and selective histamine H3 receptor ligands
  作者：Katarzyna Szczepańska、Tadeusz Karcz、Agata Siwek、Kamil J. Kuder、Gniewomir Latacz、Marek Bednarski、Małgorzata Szafarz、Stefanie Hagenow、Annamaria Lubelska、Agnieszka Olejarz-Maciej、Michał Sobolewski、Kamil Mika、Magdalena Kotańska、Holger Stark、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bioorg.2019.103071

  日期：2019.10

  meta analogues. Interestingly, benzophenone derivative 18 showed the highest affinity among all tested compounds (hH3R Ki = 3.12 nM). The likely protein-ligand interactions, responsible for their high affinity were demonstrated using molecular modeling techniques. Furthermore, selectivity, intrinsic activity at H3R, as well as drug-like properties of selected ligands were evaluated using in vitro methods

  具有变化的烷基接头长度和东部取代基的一系列新的4-吡啶基哌嗪衍生物被证明是在纳摩尔浓度范围内有效的组胺H 3受体（hH 3 R）配体。在关注其烷基连接基长度的同时，具有六个亚甲基连接基的衍生物往往比其五个亚甲基同系物更有效。此外，就苯氧基乙酰基和苯氧基丙酰基衍生物而言，八个亚甲基连接基的活性均低于其七个亚甲基同系物。然而，在对烷基接头长度影响的收集数据的整体分析中，三个亚甲基同系物似乎是最高的hH 3。到目前为止，我们小组中所有已描述的4-吡啶基哌嗪衍生物之间的R亲和力。就联苯和二苯甲酮衍生物而言，具有对位取代的第二芳族环的化合物比其间类似物具有更高的亲和力。有趣的是，二苯甲酮衍生物18在所有测试的化合物中显示出最高的亲和力（hH 3 R K i  = 3.12 nM）。使用分子建模技术证明了造成其高亲和力的可能的蛋白质-配体相互作用。此外，使用体外方法评估了选择性，在H 3 R上的固有活性以及所选配体的类药物特性。
• Calixarene ionic liquids: excellent phase transfer catalysts for nucleophilic substitution reaction in water
  作者：Fafu Yang、Hongyu Guo、Ziyu Jiao、Congcong Li、Jinqi Ye

  DOI：10.1007/s13738-011-0027-6

  日期：2012.6

  calixarene ionic liquids 3 and 6 with 3D-shaped cavities were obtained in high yields by reacting calix[4]arene or thiacalix[4]arene with 1,6-dibromohexane and then refluxing in 1-methylimidazole. The experiments of phase transfer catalysis in water suggested that they possessed excellent catalytic properties of aromatic nucleophilic substitution reaction and benzyl nucleophilic substitution. The optimized

  通过使杯[4]芳烃或噻唑杯[4]芳烃与1,6-二溴己烷反应，然后在1-甲基咪唑中回流，以高收率获得具有3D形腔的杯芳烃离子液体3和6的第一个实例。水中的相转移催化实验表明，它们具有优异的芳族亲核取代反应和苄基亲核取代反应的催化性能。在温和的反应条件下，催化反应中产物的最佳收率高达约97％。杯芳烃骨架的空腔在催化中起关键作用，并且稳定的锥体构象有利于催化。