1,3-bis(5-bromopentyl)-6-methyluracil | 56899-24-2

• 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(5-bromopentyl)-6-methyluracil
• 英文别名: 1,3-Bis(5-bromopentyl)-6-methylpyrimidine-2,4(1H,3H)-dione；1,3-bis(5-bromopentyl)-6-methylpyrimidine-2,4-dione
• CAS: 56899-24-2
• 化学式: C₁₅H₂₄Br₂N₂O₂
• 分子量: 424.176
• InChiKey: GKLWEUSPZFWTIO-UHFFFAOYSA-N

物化性质

• 沸点：
  471.5±55.0 °C(Predicted)
• 密度：
  1.445±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 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(5-bromopentyl)-6-methyluracil 在 sodium sulfide 、 四丁基硫酸氢铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以31%的产率得到16-methyl-7-thia-1,13-diazabicyclo[11.3.1]heptadec-15-ene-14,17-dione
  参考文献：
  名称：

  Structure and properties of macrocyclic compounds containing a pyrimidine fragment

  摘要：

  The structure of a series of macrocyclic compounds consisting of a pyrimidine or 1,3,5-triazine ring and an aza-or thiapolymethylene bridge connecting the N-1 and N-3 atoms of the heteroring is discussed. Some macroheterocycles undergo methylation at the sulfur atom by the action of methyl p-toluenesulfonate. The length of the polymethylene bridge determines conformation of the macroring. Compounds with a shorter bridge both in crystal and in solution are characterized by closely located structural fragments, while extension of the polymethylene chain gives rise to an unfolded structure. Conformational changes in solution are promoted by protonation of the bridging nitrogen atom, and deprotonation restores the initial structure of the macroring. The basicity of the bridging nitrogen atom depends on the geometric parameters of the macroring.

  DOI：

  10.1134/s1070428008060195
• 作为产物：
  描述：

  6-甲基尿嘧啶 以55%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

• 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。
• Macrocyclic derivatives of 6-methyluracil as ligands of the peripheral anionic site of acetylcholinesterase
  作者：Vyacheslav E. Semenov、Rashit Kh. Giniyatullin、Sofya V. Lushchekina、Ekaterina D. Kots、Konstantin A. Petrov、Alexandra D. Nikitashina、Oksana A. Minnekhanova、Vladimir V. Zobov、Evgeny E. Nikolsky、Patrick Masson、Vladimir S. Reznik

  DOI：10.1039/c4md00225c

  日期：——

  selectivity for human acetylcholinesterase (AChE), with an inhibitory power 100–200 times higher than for human butyrylcholinesterase (BChE). Docking simulations indicate specific binding of pyrimidinophanes 2a and 4 onto the peripheral anionic site of AChE. Other compounds bind to the active center of AChE as well as to the peripheral anionic site. These compounds are dual binding site inhibitors. Pyrimidinophane

  制备了具有两个邻-硝基苄基乙基二烷基铵头与不同间隔基桥接的新型嘧啶并烷。嘧啶二烯醚2a，2b和3是胆碱酯酶的可逆抑制剂。它们显示出对人乙酰胆碱酯酶（AChE）的很好的选择性，其抑制力比对人丁酰胆碱酯酶（BChE）高100-200倍。对接模拟表明嘧啶二烷2a和4与AChE的外围阴离子位点有特异性结合。其他化合物与AChE的活性中心以及周围的阴离子位点结合。这些化合物是双重结合位点抑制剂。嘧啶二烷2b及其无环对应物1在重症肌无力的动物模型中进行了测试，可以被认为是治疗病理性肌无力综合征的有价值的候选药物。
• 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。
• Synthesis and structures of pyrimidinophanes containing a nitrogen atom in the bridge
  作者：V. E. Semenov、A. E. Nikolaev、L. F. Galiullina、O. A. Lodochnikova、I. A. Litvinov、A. P. Timosheva、V. E. Kataev、Yu. Ya. Efremov、D. R. Sharafutdinova、A. V. Chernova、Sh. K. Latypov、V. S. Reznik

  DOI：10.1007/s11172-006-0292-1

  日期：2006.3

  The reactions of 1,3-bis(5-bromopentyl)-5-methyl-or 1,3-bis(5-bromopentyl)-6-methyl-uracil with benzylamine afforded pyrimidinophanes containing the nitrogen atom in the polymethylene bridge. Single-crystal X-ray diffraction study and NMR and UV spectroscopic study in solution demonstrated that the phenyl and uracil fragments in the macrocycles are in spatial proximity. Unlike the known macrocycles containing the pyrimidine ring, the pyrimidinophanes under study are conformationally rigid.

  1,3-双(5-溴戊基)-5-甲基-或1,3-双(5-溴戊基)-6-甲基-尿嘧啶与苄胺的反应产生了嘧啶并环，其中氮原子位于聚亚甲基桥上。单晶X射线衍射研究以及溶液中的核磁共振和紫外光谱研究证明，大环中的苯基和尿嘧啶片段在空间上接近。与已知的大环含有嘧啶环不同，正在研究的嘧啶并环在构象上是刚性的。