5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine | 1378943-51-1

• 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-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine
• 英文别名: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-5-[4-[4-(trifluoromethoxy)phenyl]buta-1,3-diynyl]pyrimidine-2,4-dione；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-[4-[4-(trifluoromethoxy)phenyl]buta-1,3-diynyl]pyrimidine-2,4-dione
• CAS: 1378943-51-1
• 化学式: C₂₀H₁₅F₃N₂O₆
• 分子量: 436.344
• InChiKey: NTTMEUSYNQUZPT-GVDBMIGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  二乙酰基-2'脱氧尿苷 在 甲醇 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 ammonium cerium (IV) nitrate 、 nickel(II) chloride hexahydrate 、 四甲基乙二胺 、 四丁基氟化铵 、 氨 、 碘 、 氧气 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.0h， 生成 5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis and antiviral evaluation of C5-substituted-(1,3-diyne)-2′-deoxyuridines

  摘要：

  Starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown C5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed C-H activation between two terminal alkynes, in yields ranging from 19% to 67%. Their antiviral activities were measured against a large number of DNA and RNA viruses including herpes simplex virus type 1 and type 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. The 5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine (26) is the most potent inhibitor of this series against VZV with an EC50 of similar to 1 mu M and a CC50 of 55 mu M. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including influenza virus A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and vesicular stomatitis, coxsackie B4 and respiratory syncytial virus in HeLa cell cultures and against human immunodeficiency virus type 1 and 2 in CEM cell cultures, with no specific antiviral effect. This class of compounds could be of further interest for lead optimization as anti-infectious (i.e. herpetic) agents. (C) 2012 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2012.04.001

文献信息

• Synthesis and antiviral evaluation of C5-substituted-(1,3-diyne)-2′-deoxyuridines
  作者：Ozkan Sari、Vincent Roy、Jan Balzarini、Robert Snoeck、Graciela Andrei、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2012.04.001

  日期：2012.7

  Starting from acetylated 5-ethynyl-2'-deoxyuridine (3), 14 hitherto unknown C5-substituted-(1,3-diyne)-2'-deoxyuridines (with cyclopropyl, hydroxymethyl, methylcyclopentane, p-(substituted)phenyl and disubstituted-phenyl substituents) have been synthesized via a nickel-copper catalyzed C-H activation between two terminal alkynes, in yields ranging from 19% to 67%. Their antiviral activities were measured against a large number of DNA and RNA viruses including herpes simplex virus type 1 and type 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. The 5-[4-(4-trifluoromethoxyphenyl)buta-1,3-diynyl]-2'-deoxyuridine (26) is the most potent inhibitor of this series against VZV with an EC50 of similar to 1 mu M and a CC50 of 55 mu M. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including influenza virus A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and vesicular stomatitis, coxsackie B4 and respiratory syncytial virus in HeLa cell cultures and against human immunodeficiency virus type 1 and 2 in CEM cell cultures, with no specific antiviral effect. This class of compounds could be of further interest for lead optimization as anti-infectious (i.e. herpetic) agents. (C) 2012 Published by Elsevier Masson SAS.