5-((4-tert-butylphenyl)ethynyl)-2'-deoxyuridine | 596107-17-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5-((4-tert-butylphenyl)ethynyl)-2'-deoxyuridine
• 英文别名: 5-[(4-tert-butylphenyl)ethynyl]-2'-deoxyuridine；5-[4-(tert-butyl)phenyl]ethynyl-2'-deoxyuridine；5-[2-(4-tert-butylphenyl)ethynyl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione
• CAS: 596107-17-4
• 化学式: C₂₁H₂₄N₂O₅
• 分子量: 384.432
• InChiKey: LEHRCUIPNXWRPN-RCCFBDPRSA-N

物化性质

• 熔点：
  178-182 °C
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-((4-tert-butylphenyl)ethynyl)-2'-deoxyuridine 在 N-碘代丁二酰亚胺 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以74%的产率得到3-(2'-deoxy-β-D-ribofuranosyl)-5-iodo-6-(4-tert-butylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  5-Endo-Dig Electrophilic Cyclization of α-Alkynyl Carbonyl Compounds:  Synthesis of Novel Bicyclic 5-Iodo- and 5-Bromofuranopyrimidine Nucleosides

  摘要：

  5-Endo-dig electrophilic cyclization of 5-alkynyl-2'-deoxyuridines with N-iodosuccinimide or N-bromosuccinimide in acetone at room temperature gives 3-(2'-deoxy-beta-D-ribofuranosyl)-5-halo-2,3-dihydrofuro[2,3-d]pyrimidin-2-ones that usually precipitate from the reaction mixture (86-74%).

  DOI：

  10.1021/jo0345648
• 作为产物：
  描述：

  5-(trimethylsilyl)ethynyl-2'-deoxyuridine 在 ammonium hydroxide 、 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 5-((4-tert-butylphenyl)ethynyl)-2'-deoxyuridine
  参考文献：
  名称：

  Bicyclic nucleoside inhibitors of Varicella–Zoster virus: The effect of branching in the p-alkylphenyl side chain

  摘要：

  Further to the discovery of bicyclic furanopyrimidine nucleoside analogues (BCNAs) as potent anti-VZV agents, a branched series of this family of compounds was synthesised. The aim was to study the impact of the geometry and steric hindrance in the side chain as well as lipophilic role of this moiety on biological activity. The results showed a detrimental effect of branching on antiviral activity, with a different magnitude depending on the position of branching in the side chain. This study again showed the importance of this moiety for biological activity, as well as the limited efficacy of the ClogP value as a tool for predicting the potency of BCNAs, while suggesting an alternative rationale behind the design of future series. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.071

文献信息

• Metallo-nucleosides: synthesis and biological evaluation of hexacarbonyl dicobalt 5-alkynyl-2′-deoxyuridines
  作者：Craig D. Sergeant、Ingo Ott、Adam Sniady、Srinivasarao Meneni、Ronald Gust、Arnold L. Rheingold、Roman Dembinski

  DOI：10.1039/b713371e

  日期：——

  Reactions of 5-alkynyl-2'-deoxyuridines with dicobalt octacarbonyl Co2(CO)8 in THF at room temperature gave hexacarbonyl dicobalt nucleoside complexes (77-93%). The metallo-nucleosides were characterized, including an X-ray structure of a 1-cyclohexanol derivative. In crystalline form, the Co-Co bond is perpendicular to the plane of the uracil base, which is found in the anti position. The level of

  室温下，5-炔基-2'-脱氧尿苷与二钴二羰基八羰基Co2（CO）8在THF中的反应得到六羰基二钴核苷配合物（77-93％）。表征金属核苷，包括1-环己醇衍生物的X射线结构。呈晶体形式时，Co-Co键垂直于尿嘧啶碱基的平面，该位置位于反位。检查了MCF-7和MDA-MB-231人乳腺癌细胞系的生长抑制水平，并将其与使用炔基核苷前体获得的结果进行了比较。钴化合物显示出良好的抗增殖活性，IC50值在5-50 microM的范围内。有趣的是，二甲双羰基羰基部分与5-炔基-2'的配位 -脱氧尿苷导致炔烃的非核苷侧的烷基/芳基取代基的细胞毒性显着增加，但是在氢（末端炔基）或甲硅烷基的情况下，观察到细胞毒性作用的降低。如使用活性和低活性靶标化合物的实施例所证明的，细胞毒性受到肿瘤细胞摄取和细胞核生物分布的显着影响。
• 5-Alkynyl-2′-deoxyuridines: Chromatography-free synthesis and cytotoxicity evaluation against human breast cancer cells
  作者：Srinivasarao Meneni、Ingo Ott、Craig D. Sergeant、Adam Sniady、Ronald Gust、Roman Dembinski

  DOI：10.1016/j.bmc.2007.01.048

  日期：2007.4

  Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides

  以5-碘-2'-脱氧尿苷为起始，一系列5-炔基-2'-脱氧尿苷（含正丙基、环丙基、1-羟基环己基、对甲苯基、对叔丁基苯基、对戊基苯基和三甲基甲硅烷基）炔烃取代基）通过钯催化（Sonogashira）偶联反应合成，然后采用简化的分离方案（产率 76-94%）。修饰核苷对 MCF-7 和 MDA-MB-231 人乳腺癌细胞的细胞毒活性已在体外测定。5-乙炔基-2'-脱氧尿苷是该系列中唯一含有末端乙炔的核苷，是最有效的抑制剂，MCF-7 的 IC(50) (microM) 为 0.4+/-0.3，MDA 为 4.4+/-0.4 -MB-231。
• Bicyclic nucleoside inhibitors of Varicella–Zoster virus: The effect of branching in the p-alkylphenyl side chain
  作者：Giovanna Luoni、Christopher McGuigan、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1016/j.bmcl.2005.05.071

  日期：2005.8

  Further to the discovery of bicyclic furanopyrimidine nucleoside analogues (BCNAs) as potent anti-VZV agents, a branched series of this family of compounds was synthesised. The aim was to study the impact of the geometry and steric hindrance in the side chain as well as lipophilic role of this moiety on biological activity. The results showed a detrimental effect of branching on antiviral activity, with a different magnitude depending on the position of branching in the side chain. This study again showed the importance of this moiety for biological activity, as well as the limited efficacy of the ClogP value as a tool for predicting the potency of BCNAs, while suggesting an alternative rationale behind the design of future series. (c) 2005 Elsevier Ltd. All rights reserved.
• 5-<i>Endo</i>-<i>D</i><i>ig</i> Electrophilic Cyclization of α-Alkynyl Carbonyl Compounds:  Synthesis of Novel Bicyclic 5-Iodo- and 5-Bromofuranopyrimidine Nucleosides
  作者：Meneni Srinivasa Rao、Noor Esho、Craig Sergeant、Roman Dembinski

  DOI：10.1021/jo0345648

  日期：2003.8.1

  5-Endo-dig electrophilic cyclization of 5-alkynyl-2'-deoxyuridines with N-iodosuccinimide or N-bromosuccinimide in acetone at room temperature gives 3-(2'-deoxy-beta-D-ribofuranosyl)-5-halo-2,3-dihydrofuro[2,3-d]pyrimidin-2-ones that usually precipitate from the reaction mixture (86-74%).