1-(3-甲氧基丙基)-6-氨基尿嘧啶 | 158893-39-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1-(3-甲氧基丙基)-6-氨基尿嘧啶
• 英文名称: 1-(3-methoxypropyl)-6-aminouracil
• 英文别名: 6-amino-1-(3-methoxypropyl)uracil；6-amino-1-(3-methoxy-propyl)-1H-pyrimidine-2,4-dione；6-Amino-1-(3-methoxy-propyl)-1H-pyrimidin-2,4-dion；6-Amino-1-(3-methoxypropyl)pyrimidine-2,4-dione
• CAS: 158893-39-1
• 化学式: C₈H₁₃N₃O₃
• mdl: MFCD06483947
• 分子量: 199.21
• InChiKey: RWSZTPQGFXCVNF-UHFFFAOYSA-N

物化性质

• 熔点：
  205-207 °C
• 密度：
  1.227±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-甲氧基丙基)-6-氨基尿嘧啶 在 碘代三甲硅烷 、 4-己基苯胺 作用下， 以 氯仿 为溶剂， 反应 14.67h， 生成 N¹,N⁶-propylene-6-(4-hexylanilino)uracil
  参考文献：
  名称：

  Molecular Modeling and Synthesis of Inhibitors of Herpes Simplex Virus Type 1 Uracil-DNA Glycosylase

  摘要：

  We recently reported the properties of the first selective inhibitors of herpes simplex virus type 1 (HSV1) uracil-DNA glycosylase (UDG), an enzyme of DNA repair that has been proposed to be required for reactivation of the virus from latency. 6-(4-Octylanilino)uracil (octAU) was the most potent inhibitor among a series of 6-(4-alkylanilino)uracils, acting in the micromolar range and without effect against human UDG. A 28.5-kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. We have used the coordinates of this structure in order to study interaction of our inhibitors with the enzyme, and a model of binding between octAU and UDG has been derived. Starting with the optimized model, the activity of several octAU analogues was predicted, and the values compared favorably with experimental results found for the synthetic compounds. Several hydrophilic derivatives were predicted and found to be active as UDG inhibitors. These compounds will be useful to determine if UDG, like the viral thymidine kinase, is required for reactivation of HSV1 from latency in nerve cells.

  DOI：

  10.1021/jm980718d
• 作为产物：
  描述：

  N-cyanoacetyl-N'-(3-methoxy-propyl)-urea 在 sodium hydroxide 作用下， 生成 1-(3-甲氧基丙基)-6-氨基尿嘧啶
  参考文献：
  名称：

  Synthesis of 1-Mono- and 1,3-Di-Substituted 6-Aminouracils. Diuretic Activity

  摘要：

  DOI：

  10.1021/jo50006a010

文献信息

• Synthesis, radiolabelling and initial biological characterisation of ¹⁸F-labelled xanthine derivatives for PET imaging of Eph receptors
  作者：Marc Pretze、Christin Neuber、Elisa Kinski、Birgit Belter、Martin Köckerling、Amedeo Caflisch、Jörg Steinbach、Jens Pietzsch、Constantin Mamat

  DOI：10.1039/d0ob00391c

  日期：——

  Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the methyl group at the uracil residue ([18F]3) rather than the methyl group of the phenoxy moiety ([18F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [18F]2 and [18F]3 and the respective tosylate precursors as

  Eph受体酪氨酸激酶，特别是EphA2和EphB4，由于它们在癌症进展和治疗抵抗中的重要作用，代表了分子成像的有希望的候选者。黄嘌呤衍生物被确定为有效的Eph受体抑制剂，IC50值在低纳摩尔范围（1-40 nm）内。这些化合物占据激酶结构域中ATP结合位点的疏水口袋。基于铅化合物1，我们设计了两种氟18标记的受体酪氨酸激酶抑制剂（[18F] 2/3）作为正电子发射断层扫描（PET）的潜在示踪剂。停靠到ATP结合位点使我们能够找到最佳的放射性标记位置。据预测，尿嘧啶残基（[18F] 3）上的甲基而不是苯氧基部分（[18F] 2）上的甲基被氟丙基取代，可以保留铅化合物1的亲和力。指出了合成[18 F] 2和[18 F] 3以及各自的甲苯磺酸酯前体的合成路线，以及插入氟18的标记程序。放射性标记后，两种放射性示踪剂均以大约5％的放射化学收率获得，且放射化学纯度高（> 98％），摩尔活性> 10
• [DE] UNSYMMETRISCH SUBSTITUIERTE XANTHINE MIT ADENOSINANTAGONISTISCHEN EIGENSCHAFTEN<br/>[EN] ASYMMETRICALLY SUBSTITUTED XANTHINE WITH ADENOSINE-ANTAGONISTIC PROPERTIES<br/>[FR] XANTHINE SUBSTITUEE ASYMETRIQUEMENT AYANT DES PROPRIETES ANTAGONISTES DE L'ADENOSINE
  申请人：BOEHRINGER INGELHEIM KG

  公开号：WO1994003456A1

  公开（公告）日：1994-02-17

  (DE) Die vorliegende Erfindung betrifft neue Xanthin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel und ihre Verwendung als Zwischenverbindungen.(EN) New xanthine derivatives, a process for preparing the same and their use as medicaments are disclosed, as well as their use as intermediate compounds.(FR) L'invention concerne de nouveaux dérivés de xanthine, leur procédé de fabrication et leur utilisation comme médicaments, ainsi que leur utilisation comme composés intermédiaires.

  该发明涉及新型蒽醌衍生物、制备它们的方法以及它们用作药品和中间化合物的用途。...(此处截稿，完整翻译未提供)
• Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A2B receptor antagonists
  作者：María Isabel Nieto、María Carmen Balo、José Brea、Olga Caamaño、María Isabel Cadavid、Franco Fernández、Xerardo García Mera、Carmen López、José Enrique Rodríguez-Borges

  DOI：10.1016/j.bmc.2009.03.029

  日期：2009.5

  In order to identify a high-affinity, selective antagonist for the A(2B) subtype adenosine receptor, more than 40 1,8-disubstituted-3-(3-methoxypropyl) xanthines were prepared and evaluated for their binding affinity at recombinant human adenosine receptors, mainly of the A(2A) and A(2B) subtypes. Some of the 1-ethyl-3-(3-methoxypropyl)-8-aryl substituted derivatives 15(a-m) showed moderate-to-high affinity at human A(2B) receptors, with compound 15d showing A(2B) selectivity over the other A receptors assayed (A(1), A(2A), A(3)) of 34-fold or over. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and use of FSCPX, an irreversible adenosine A1 antagonist, as a ‘Receptor Knock-Down’ tool
  作者：Jacqueline E.van Muijlwijk-Koezen、Henk Timmerman、Richard P.van der Sluis、Andrea C van de Stolpe、Wiro M.P.B Menge、Margot W Beukers、Piet H van der Graaf、Miriam de Groote、Adriaan P IJzerman

  DOI：10.1016/s0960-894x(01)00069-5

  日期：2001.3

  A new preparative synthetic route for the irreversible adenosine A1 antagonist 8-cyclopentyl-3-N-[3-((3-(4-fluorosulphonyl)benzoyl)-oxy)-propyl]-1-N-propyl-xanthine (FSCPX, 1) is described. The availability of ample amounts of the irreversible antagonist FSCPX allowed us to use FSCPX as a research tool for adenosine A1 receptors in in vivo experiments. After verification of the irreversible antagonistic function of FSCPX in in vitro experiments, FSCPX was used successfully as a 'receptor knock-down' tool in in vivo experiments on conscious rats.
• UNSYMMETRISCH SUBSTITUIERTE XANTHINE MIT ADENOSINANTAGONISTISCHEN EIGENSCHAFTEN
  申请人：BOEHRINGER INGELHEIM KG

  公开号：EP0654033A1

  公开（公告）日：1995-05-24