1-(8-bromooctyl)thymine | 149949-97-3

• 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-(8-bromooctyl)thymine
• CAS: 149949-97-3
• 化学式: C₁₃H₂₁BrN₂O₂
• 分子量: 317.226
• InChiKey: ZRYDEFLYJJFOBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.58
• 重原子数：
  18.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  54.86
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(8-bromooctyl)thymine 在 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 1-Phosphonooctylthymine
  参考文献：
  名称：

  Design, Synthesis, and Enzymatic Evaluation of Multisubstrate Analogue Inhibitors of Escherichia coli Thymidine Phosphorylase

  摘要：

  A series of acyclic phosphonate derivatives of thymine has been synthesized and tested as multisubstrate analogue inhibitors of Escherichia colt thymidine phosphorylase. The compounds synthesized include 1-(phosphonoalkyl)thymines with six to nine methylenes (1-4, respectively); 1-[(Z)-4-phosphonomethoxy-2-butenyl]thymine (5) and its butyl and 2,3-cis-dihydroxybutyl derivatives (6 and 7, respectively); 1-[(Z)-(4-(phosphonomethoxy)methoxy)-2-butenyl]thymine (8) and also its butyl and 2,3-cis-dihydroxybutyl analogues (9 and 10); and 1-[((Z)-4-(phosphonomethoxy)-2-butenoxy)methyl]thymine(11), Evaluation of these compounds against E. coli revealed significant enzymatic inhibition by 2, 3, 4, 6, and 8 at a concentration of 1000 mu M, 3 and 4 being the most potent. Replacement of the thymine base in 3 by 6-amino-5-bromouracil and 7-deazaxanthine afforded compounds 12 and 13, which showed a pronounced improvement of TPase inhibition, comparable to 7-deazaxanthine. When inorganic phosphate was used as a variable substrate, compounds 12 and 13 displayed competitive kinetics with respect to phosphate, indicating a direct interaction of these compounds with the phosphate binding site. Also compounds 12 and 13 were found to be competitive inhibitors of TPase against thymidine as a variable substrate. These results are consistent with the compounds being multisubstrate analogue inhibitors of E. coli TPase, and they represent the first example of such TPase inhibitors.

  DOI：

  10.1021/jm9911377
• 作为产物：
  描述：

  胸腺嘧啶 在 三甲基氯硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 1-(8-bromooctyl)thymine
  参考文献：
  名称：

  胶束中的分子识别：氢键和疏水性在 SDS 胶束中腺嘌呤-胸腺嘧啶碱基配对中的作用

  摘要：

  本文描述了一类新的分子受体 2，它们通过氢键（碱基配对）在水溶液中结合腺嘌呤衍生物 3。受体是嵌入胶束的胸腺嘧啶基团的超分子组装体，当（胸腺嘧啶烷基）铵盐 1 [Thy-(CH 2 ) n -N + Me 3 ] 与十二烷基硫酸钠 (SDS) 水溶液混合时，胶束会自组装。NMR 滴定研究和 Job 的方法表明，结合以 1:1 的腺嘌呤-胸腺嘧啶化学计量发生，其方式与胶束内的碱基配对一致。在没有 SDS 的情况下，碱基堆积优先于碱基配对

  DOI：

  10.1021/ja00070a007

文献信息

• Synthesis and evaluation of thymine-derived carboxamides against mitochondrial thymidine kinase (TK-2) and related enzymes
  作者：Eva-Marı́a Priego、Jan Balzarini、Anna Karlsson、Marı́a-José Camarasa、Marı́a-Jesús Pérez-Pérez

  DOI：10.1016/j.bmc.2004.07.036

  日期：2004.10

  employed has been a solution-phase parallel synthesis based on the coupling of three thymine-derived acids [4-(thymin-1-yl)butyric acid (I), [4-(thymin-1-yl)-butyrylamino]acetic acid (II) and 6-(thymin-1-yl)hexanoic acid (III)] with different commercially available primary amines that carry cyano and/or phenyl groups. The couplings were performed in good yields (from 60% to 90%), with the exception of those

  基于我们先前确定的线粒体胸苷激酶（TK-2）抑制剂的结构，合成了三组源自胸腺嘧啶的羧酰胺，并针对TK-2和相关酶进行了测试。所采用的方法是基于三种胸腺嘧啶衍生的酸[4-（胸苷-1-基）丁酸（I），[4-（胸苷-1-基）-丁酰氨基]偶合的溶液相平行合成。乙酸（Ⅱ）和6-（胸腺嘧啶-1-基）己酸（Ⅲ）]和带有氰基和/或苯基的可商购的不同伯胺。除掺入高度拥挤的三苯甲胺（e）的偶联剂外，偶联剂均以良好的收率（60％至90％）进行。从新合成的化合物中，N-三苯甲基-6-（胸腺嘧啶-1-基）己酰胺（IIIe）是最具活性的TK-2抑制剂（IC（50）= 19 +/- 2microM）。
• Effect of a Polymethylene Chain on the Intramolecular Hydrogen Bond between Adenine and Thymine
  作者：Toshio Itahara

  DOI：10.1246/bcsj.75.285

  日期：2002.2

  The intramolecular hydrogen bond between the adenine and thymine rings of 9-[ω-(thymin-1-yl)alkyl]adenine was investigated in chloroform by means of NMR spectroscopy. The formation of the intramolecular hydrogen bond was dependent on the length of the polymethylene chains between adenine and thymine, and the thermodynamic parameters were estimated. The length of the polymethylene chains caused a marked difference in the physical properties of the compounds.

  在氯仿中，通过核磁共振谱法研究了9-[ω-(胸苷-1-基)烷基]腺苷的腺苷环和胸苷环之间的分子内氢键形成。分子内氢键的形成依赖于腺苷和胸苷之间聚亚甲基链的长度，并估算了热力学参数。聚亚甲基链的长度导致化合物的物理性质产生明显差异。
• Fluorescent molecular rotors as sensors for the detection of thymidine phosphorylase
  作者：Manuela Petaccia、Luisa Giansanti、James N. Wilson、Heajin Lee、Sara Battista、Giovanna Mancini

  DOI：10.1016/j.bmc.2020.115881

  日期：2021.1

  to detect and quantify them. The three molecular rotors developed as TP sensors differ in the length of the alkylic spacer joining the ligand unit, a thymine moiety, and the fluorescent molecular rotor, a [4-(1-dimethylamino)phenyl]-pyridinium bromide. Their ability to trigger an optical signal upon the interaction with thymidine phosphorylase was investigated by fluorescent measurements.

  合成了三个新的荧光分子转子，目的是将它们用作传感器来给药胸苷磷酸化酶，这是 5-氟尿嘧啶的靶酶之一，5-氟尿嘧啶是一种有效的化疗药物，主要用于治疗许多实体瘤，通过阻碍新陈代谢发挥作用嘧啶。5-氟尿嘧啶的治疗窗很窄，事实上，其最佳剂量与其靶酶水平密切相关，患者之间差异很大，因此最重要的是有一种简单快速的方法来检测和量化它们。 开发为 TP 传感器的三个分子转子在连接配体单元、胸腺嘧啶部分和荧光分子转子、[4-(1-二甲基氨基)苯基]-溴化吡啶鎓的烷基间隔的长度上有所不同。通过荧光测量研究了它们在与胸苷磷酸化酶相互作用时触发光信号的能力。
• NMR and UV Study of 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[thymine] and 1,1′-(<i>α</i>,<i>ω</i>-Alkanediyl)bis[uracil]
  作者：Toshio Itahara

  DOI：10.1246/bcsj.70.2239

  日期：1997.9

  Treatment of thymine or uracil with Br(CH2)nBr (n = 3—10) in the presence of t-BuOK gave 1,1′-(α,ω-alkanediyl)bis[thymine] or 1,1′-(α,ω-alkanediyl)bis[uracil] together with 1-(ω-bromoalkyl)thymine or 1-(ω-bromoalkyl)uracil. The structures of these products were determined on the basis of the coupling constants between 5- and 3-positions of uracil ring on the 1H NMR spectra. Molecular aggregation of the thymine and uracil rings of these compounds in aqueous solution was studied on the basis of their 1H NMR and UV spectra. A stacking interaction of the two thymine rings linked by shorter polymethylene chains such as trimethylene and tetramenthylene groups was observed.

  将胸腺嘧啶或尿嘧啶与Br(CH2)nBr（n = 3—10）在t-BuOK存在下处理，得到了1,1′-(α,ω-烷烃二基)双[胸腺嘧啶]或1,1′-(α,ω-烷烃二基)双[尿嘧啶]，以及1-(ω-溴烷基)胸腺嘧啶或1-(ω-溴烷基)尿嘧啶。这些产物的结构是基于尿嘧啶环中5位和3位之间的耦合常数在1H NMR光谱上的分析来确定的。基于它们的1H NMR和紫外光谱，研究了这些化合物在水溶液中胸腺嘧啶和尿嘧啶环的分子聚集情况。观察到由较短的聚亚 methylene 链（如三亚甲基和四亚甲基基团）连接的两个胸腺嘧啶环之间存在堆叠相互作用。
• Molecular recognition in aqueous micellar solution: adenine-thymine base-pairing in SDS micelles
  作者：James S. Nowick、Jenny S. Chen

  DOI：10.1021/ja00029a060

  日期：1992.1