1,3-bis(6-bromohexyl)-6-methyluracil | 63550-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1,3-bis(6-bromohexyl)-6-methyluracil
• 英文别名: 1,3-Bis(6-bromohexyl)-6-methylpyrimidine-2,4(1H,3H)-dione；1,3-bis(6-bromohexyl)-6-methylpyrimidine-2,4-dione
• CAS: 63550-42-5
• 化学式: C₁₇H₂₈Br₂N₂O₂
• 分子量: 452.23
• InChiKey: UEECRCJRKLVWFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-bis(6-bromohexyl)-6-methyluracil 在 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 39.0h， 生成 18,34-dimethyl-8,26-diethyl-8,26-di-n-decyl-1,8,15,19,26,33-hexaazatricyclo[31,3,1,1^15,19]-octatriaconta-17,34-diene-16,36,37,38-tetraone dibromide
  参考文献：
  名称：

  Antibacterial and antifungal activity of acyclic and macrocyclic uracil derivatives with quaternized nitrogen atoms in spacers

  摘要：

  The reactions of 1,3-bis(alpha,omega-bromoalkyl)-6-methyluracils with 1,3-bis(alpha,omega-ethylaminoalkyl)-6-methyluracils or 1,3-bis(bromopentyl)thymine with butylamine afforded pyrimidinophanes containing one or two uracil units and nitrogen atoms in bridging polymethylene chains. In some cases individual geometric isomers of pyrimidinophanes differing in the mutual arrangement of the carbonyl and methyl groups at different pyrimidine rings were isolated. Quaternization of the bridging nitrogen atom with o-nitrobenzyl bromide, benzyl bromide, n-decyl bromide gave rise to water-soluble pyrimidinophanes which were evaluated for their antibacterial and antifungal activity. The arrangement of the carbonyl groups in macrocycles doesn't affect the activity. Antibacterial and antifungal activity of pyrimidinophanes increases with the increase of polymethylene N-(pyr)-N-chain length and dramatically increases upon the introduction of n-decyl substituent at nitrogen atoms in spacers. Pyrimidi-nophanes with 5 and 6 methylene groups in N(pyr)-N-chain and n-decyl substituent showed significant bacteriostatic, fungistatic, bactericidal, fungicidal activity which comparable with standard antibacterial and antifungal drugs. Acyclic counterpart demonstrated the highest activity against fungi. Toxicity of more effective pyrimidinophanes was determined for mice and Daphnia magna Straus. (c) 2006 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.03.030
• 作为产物：
  描述：

  6-甲基尿嘧啶 以50%的产率得到
  参考文献：
  名称：

  REZNIK V. S.; SALIXOV I. SH.; SHVETSOV YU. S.; SHIRSHOV A. N.; BAKULIN V.+, IZV. AN CCCP. CEP. XIM., 1977, HO 4, 880-884

  摘要：

  DOI：

文献信息

• Metal binding properties of pyrimidinophanes and their acyclic counterparts
  作者：Sergey N. Podyachev、Vyacheslav E. Semenov、Victor V. Syakaev、Nadezda E. Kashapova、Svetlana N. Sudakova、Julia K. Voronina、Anatoly S. Mikhailov、Alexandra D. Voloshina、Vladimir S. Reznik、Alexander I. Konovalov

  DOI：10.1039/c3ra47571a

  日期：——

  A series of acyclic and macrocyclic nucleobase derivatives that contain uracil and 2-thiocytosine units linked by polymethylene spacers was prepared. The length of spacers as well as the oxidation number of sulfur atoms entering into the structure of the compounds was varied. The crystal structure of pyrimidinophane with hexa- and heptamethylene linkers was established by X-ray analysis. The metal ion-binding properties of pyrimidinophanes and their acyclic counterparts were investigated by liquid extraction and 1H NMR titration experiments. The compounds with 2-thiocytosine fragments revealed a high selectivity of extraction towards Ag+ ions. The stoichiometry of silver complexes and the binding constants have been determined. The antibacterial activity of these complexes was also discussed.

  一系列含有尿嘧啶和2-硫胞嘧啶单元并通过聚亚甲基间隔相连的非环和宏环核碱衍生物被制备出来。间隔的长度以及进入化合物结构的硫原子的氧化数被改变。通过X射线分析确定了含有六亚甲基和七亚甲基连接体的嘧啶冠醚的晶体结构。通过液体萃取和1H NMR滴定实验研究了嘧啶冠醚及其非环对应物的金属离子结合性质。含有2-硫胞嘧啶片段的化合物显示出对Ag+离子的高选择性萃取。确定银络合物的化学计量比和结合常数。这些络合物的抗菌活性也进行了讨论。
• Novel Acetylcholinesterase Inhibitors Based on Uracil Moiety for Possible Treatment of Alzheimer Disease
  作者：Vyacheslav E. Semenov、Irina V. Zueva、Marat A. Mukhamedyarov、Sofya V. Lushchekina、Elena O. Petukhova、Lilya M. Gubaidullina、Evgeniya S. Krylova、Lilya F. Saifina、Oksana A. Lenina、Konstantin A. Petrov

  DOI：10.3390/molecules25184191

  日期：——

  compounds indicated that they could function as dual binding site acetylcholinesterase inhibitors, binding to both the peripheral anionic site and active site. The data from in vitro experiments show that the most active compounds exhibit affinity toward acetylcholinesterase within a nanomolar range, with selectivity for acetylcholinesterase over butyrylcholinesterase reaching four orders of magnitude.

  在这项研究中，合成了基于 6-甲基尿嘧啶和缩合尿嘧啶的新型衍生物，即 2,4-喹唑啉-2,4-二酮，在嘧啶环的 N 原子上具有 ω-（邻腈苄基乙氨基）烷基链。在这一系列合成的化合物中，多亚甲基链从具有四亚甲基链到六亚甲基链不等，并且在链中引入了仲NH、叔乙基氨基和季铵基团。化合物的分子模型表明它们可以作为双结合位点乙酰胆碱酯酶抑制剂，与外周阴离子位点和活性位点结合。体外实验数据表明，活性最强的化合物对乙酰胆碱酯酶的亲和力在纳摩尔范围内，乙酰胆碱酯酶的选择性比丁酰胆碱酯酶高四个数量级。体内生物测定证明了这些化合物在使用阿尔茨海默病动物模型治疗记忆障碍方面的效力。
• Unusual Reaction of Macrocyclic Uracils with Paraformaldehyde
  作者：Vyacheslav E. Semenov、Rashit Kh. Giniyatullin、Anatoly S. Mikhailov、Anton E. Nikolaev、Sergey V. Kharlamov、Shamil K. Latypov、Vladimir S. Reznik

  DOI：10.1002/ejoc.201100985

  日期：2011.10

  The ability of simple uracils to afford bis(uracil-5-yl)methanes upon reaction with paraformaldehyde is well documented. This reaction has been used in the preparation of pyrimidinophanes. The extension of the scope of this reaction to the synthesis of multipyrimidinophanes has been reported. Starting with isomeric pyrimidinophane containing 6-methyluracil and 5-methyluracil (thymine) moieties, linearly

  简单的尿嘧啶在与多聚甲醛反应后提供双（尿嘧啶-5-基）甲烷的能力已得到充分证明。该反应已用于制备嘧啶烷。已报道将该反应的范围扩展到多嘧啶烷的合成。以含有 6-甲基尿嘧啶和 5-甲基尿嘧啶（胸腺嘧啶）部分的异构嘧啶并烷为起始，制备了线性排列的多大环。一个完全出乎意料的结果是，含有 6-甲基尿嘧啶部分的异构嘧啶烷与多聚甲醛的反应仅产生环状排列的大环，特别是具有环状拓扑结构的穴状嘧啶和多嘧啶。
• 6-Methyluracil Derivatives as Bifunctional Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease
  作者：Vyacheslav E. Semenov、Irina V. Zueva、Marat A. Mukhamedyarov、Sofya V. Lushchekina、Alexandra D. Kharlamova、Elena O. Petukhova、Anatoly S. Mikhailov、Sergey N. Podyachev、Lilya F. Saifina、Konstantin A. Petrov、Oksana A. Minnekhanova、Vladimir V. Zobov、Evgeny E. Nikolsky、Patrick Masson、Vladimir S. Reznik

  DOI：10.1002/cmdc.201500334

  日期：2015.11

  6‐methyluracil derivatives are able to penetrate the blood–brain barrier (BBB), inhibiting brain‐tissue AChE. The most potent AChE inhibitor, 3 d (1,3‐bis[5‐(o‐nitrobenzylethylamino)pentyl]‐6‐methyluracil), was found to improve working memory in scopolamine and transgenic APP/PS1 murine models of Alzheimer's disease, and to significantly decrease the number and area of β‐amyloid peptide plaques in the brain

  设计并合成了在嘧啶环的氮原子上具有ω-（取代的苄基乙基氨基）烷基链的新型6-甲基尿嘧啶衍生物。烷基链中亚甲基的数目与苄环上的吸电子取代基一起变化。这些化合物是胆碱酯酶的混合型可逆抑制剂，其中一些对人乙酰胆碱酯酶（hAChE）表现出显着的选择性，其抑制力在纳摩尔范围内，比人丁酰胆碱酯酶（hBuChE）高出1万倍以上。分子模型研究表明，这些化合物是双功能AChE抑制剂，跨越酶的活性位点峡谷并与其外围阴离子位点（PAS）结合。体内实验表明，6-甲基尿嘧啶衍生物能够穿透血脑屏障（BBB），从而抑制脑组织AChE。最有效的AChE抑制剂，3 d（1,3-双[5-（邻硝基苄基乙基氨基）戊基] -6-甲基尿嘧啶）被发现可以改善东pol碱和阿尔茨海默氏病转基因APP / PS1鼠模型的工作记忆，并显着减少数量和脑中β淀粉样蛋白斑块的面积。
• Reaction of 6-methyluracyl derivatives with acetylacetone and ethyl acetoacetate
  作者：E. S. Krylova、V. E. Semenov、I. V. Galyametdinova、D. R. Sharafutdinova、V. D. Akamsin、V. S. Reznik

  DOI：10.1134/s1070363210070248

  日期：2010.7

  Reaction of acetylacetone and ethyl acetoacetate with 1-(ω-bromoalkyl)-3,6-dimethyluracyls and 1,3-bis(ω-bromoalkyl)-6-methyluracyls lead to the formation of uracyl derivatives containing the ketone and ketoester fragments. Conditions leading to the highest yields of the compounds synthesized were found.

  乙酰丙酮和乙酰乙酸乙酯与1-（ω-溴烷基）-3,6-二甲基尿嘧啶和1,3-双（ω-溴烷基）-6-甲基尿嘧啶的反应导致形成含有酮和酮酯片段的尿嘧啶衍生物。发现了导致最高产率的合成化合物的条件。