1,3-bis(ω-bromobutyl)-6-methyluracil | 60316-18-9

• 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(ω-bromobutyl)-6-methyluracil
• 英文别名: 1,3-bis(4-bromobutyl)-6-methyluracil；1,3-bis(4-bromobutyl)-6-methylpyrimidine-2,4(1H,3H)-dione；1,3-bis(4-bromobutyl)-6-methylpyrimidine-2,4-dione
• CAS: 60316-18-9
• 化学式: C₁₃H₂₀Br₂N₂O₂
• 分子量: 396.122
• InChiKey: VWLPDCZRYYZYCU-UHFFFAOYSA-N

物化性质

• 熔点：
  64-66 °C
• 沸点：
  448.2±55.0 °C(Predicted)
• 密度：
  1.521±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 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(ω-bromobutyl)-6-methyluracil 在 potassium carbonate 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 127.0h， 生成 6,20-diethyl-14,28-dimethyl-1,6,11,15,20,25-hexaazatricyclo[23.3.1.1^11,15]triaconta-13,27-diene-12,26,29,30-tetraone
  参考文献：
  名称：

  摘要：

  The reactions of 1,3-bis(omega-bromobutyl- or -pentyl)-6-methyluracil with 1,3-bis(omega-ethyl-aminobutyl- or -pentyl)-6-methyluracil afforded pyrimidinophanes containing N atoms in bridging polymethylene chains. Individual geometric isomers of pyrimidinophanes were isolated. The structure of one of these isomers was established by X-ray diffraction analysis. Quaternization of the bridging N atoms with o-nitrobenzyl bromide gave rise to water-soluble pyrimidinophanes.

  DOI：

  10.1023/a:1025653328231
• 作为产物：
  描述：

  6-甲基尿嘧啶 、 1,4-二溴丁烷 以48%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。
• 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。
• Reactions of 1,3-bis(ω-bromoalkyl)-6-methyluracils with 2-(dialkylamino)ethylphosphonates and 2-(dialkylamino)ethyl phosphates
  作者：V. S. Reznik、V. D. Akamsin、I. V. Galyametdinova

  DOI：10.1007/bf02494909

  日期：2000.6

  Abstract1,3-Bis(4-bromobutyl)-6-methyluracil reacts with diethyl 2-(dimethylamino)ethylphosphonate to form a bisquaternary ammonium salt, whereas the reaction of 1,3-bis-(6-bromohexyl)-6-methyluracil with diethyl 2-(diethylamino)ethyl phosphate gives 1,3-bis-[(6-diethoxyphosphoryloxy)hexyl]-6-methyluracil and 1,1,4,4-tetraethylpiperazinium dibromide.

  摘要 1,3-双(4-溴丁基)-6-甲基尿嘧啶与2-(二甲氨基)乙基膦酸二乙酯反应生成双季铵盐，而1,3-双-(6-溴己基)-6-甲基尿嘧啶与2-(二乙氨基)乙基磷酸二乙酯得到1,3-双-[(6-二乙氧基磷酰氧基)己基]-6-甲基尿嘧啶和1,1,4,4-四乙基哌嗪二溴化物。
• Novel Uracil-Based Inhibitors of Acetylcholinesterase with Potency for Treating Memory Impairment in an Animal Model of Alzheimer’s Disease
  作者：Vyacheslav E. Semenov、Irina V. Zueva、Sofya V. Lushchekina、Eduard G. Suleimanov、Liliya M. Gubaidullina、Marina M. Shulaeva、Oksana A. Lenina、Konstantin A. Petrov

  DOI：10.3390/molecules27227855

  日期：——

  Novel derivatives based on 6-methyluracil and condensed uracil, 2,4-quinazoline-2,4-dione, were synthesized with terminal meta- and para-benzoate moieties in polymethylene chains at the N atoms of the pyrimidine ring. In the synthesized compounds, the polymethylene chains were varied from having tris- to hexamethylene chains and quaternary ammonium groups; varying substituents (ester, salt, acid) at

  基于 6-甲基尿嘧啶和缩合尿嘧啶 2,4-喹唑啉-2,4-二酮的新型衍生物在嘧啶环的 N 原子处的聚亚甲基链中合成了末端间苯甲酸酯和对苯甲酸酯部分。在合成的化合物中，多亚甲基链从具有三亚甲基链到六亚甲基链和季铵基团不等；苯环上的不同取代基（酯、盐、酸）被引入链和苯甲酸酯部分。体内生物学实验证明了这些化合物在减少 β-淀粉样斑块数量方面的效力及其在阿尔茨海默病转基因模型中治疗记忆障碍的适用性。
• ——
  作者：R. R. Shagidullin

  DOI：10.1023/a:1023348019891

  日期：——

  A new macrocycle including pyrimidine fragments, 12,23,36-trimethyl-24,40-dioxo-15,33-dithia-2,9,13,22,26,35,38,39-octaazatetracyclo[32.3. 1.1(10,14), 1(22,26)] tetraconta-1(38),10(39),11,13,23,34,36-heptaene, was synthesized. According to the data of IR and UV spectroscopy and HF/6-31G** quantum-chemical calculations, macrocyclic compounds of this series in crystal exist in the amino form, one NH group of which is likely to be involved in intramolecular hydrogen bond, and the other, in intermolacular hydrogen bond. The strength of the latter depends on the macroring size. In solution, the above structures are supplemented by conformers containing both intramolecularly H-bonded and free amino groups, predominantly with trans structure of the H-N-C=N fragment. The imino form of the aminopyrimidine moieties is hardly probable.