1-(1-C-cyano-2-deoxy-β-D-erythro-pentofuranosyl)uracil | 153959-84-3

• 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: 1-(1-C-cyano-2-deoxy-β-D-erythro-pentofuranosyl)uracil
• 英文别名: 1'-cyano-2'-deoxyuridine；CNdU；(2S,4S,5R)-2-(2,4-dioxopyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)oxolane-2-carbonitrile
• CAS: 153959-84-3
• 化学式: C₁₀H₁₁N₃O₅
• 分子量: 253.214
• InChiKey: WSAVHPNHJULPSY-PJKMHFRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(1-C-cyano-2-deoxy-β-D-erythro-pentofuranosyl)uracil 在 吡啶 、 4,4'-双甲氧基三苯甲基氯 作用下， 反应 1.0h， 以87%的产率得到(2S,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-hydroxytetrahydrofuran-2-carbonitrile
  参考文献：
  名称：

  Competitive Inhibition of Uracil DNA Glycosylase by a Modified Nucleotide Whose Triphosphate is a Substrate for DNA Polymerase

  摘要：

  Base excision repair (BER) enzymes are attractive targets for antiviral and anticancer agents. A number of nucleotides and nucleotide analogues are potent competitive inhibitors of BER glycosylases when they are incorporated into synthetic oligonucleotides. However, these molecules often are not substrates for DNA polymerases, which limits their utility in cells and as potential therapeutic agents. 1'-Cyano-2'-deoxyuridine (CNdU) is a nanomolar competitive inhibitor of uracil DNA glycosylase. In addition, the respective nucleotide triphosphate is accepted as a substrate by the Klenow fragment (exo-) of DNA polymerase I from E. coli. This is the first competitive inhibitor of UDG that is incorporated into DNA by Klenow exo-, a model replicative polymerase. 1'-Cyano-2'-deoxyuridine (CNdU) and related molecules may prove useful as a new family of therapeutic or experimental agents that target DNA repair by using the cells' polymerase(s) to incorporate them into DNA. A potential benefit of such a mechanism is that multiple incorporations can occur for longer DNA molecules leading to amplification of the inhibitory effect beyond that seen here with short DNA duplexes.

  DOI：

  10.1021/ja807705z
• 作为产物：
  描述：

  1'-cyano-2'-deoxy-2'β-bromouridine 在 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 4.0h， 生成 1-(1-C-cyano-2-deoxy-β-D-erythro-pentofuranosyl)uracil
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 1′-C-Cyano-Pyrimidine Nucleosides

  摘要：

  2'-Deoxy-, 2'-bromo-, and arabine-1'-C-cyano-pyrimidine nucleosides were synthesized from O-2,2'-cyclouridine. Incorporation of cyano group at the anomeric position was achieved by treatment of 1',2'-unsaturated uridine with NBS in the presence of pivalic acid followed by TMS-cyanide and stannic chloride. Antineoplastic and antiviral activities of those compounds are also discussed.

  DOI：

  10.1080/07328319608002386

文献信息

• Competitive Inhibition of Uracil DNA Glycosylase by a Modified Nucleotide Whose Triphosphate is a Substrate for DNA Polymerase
  作者：Haidong Huang、James T. Stivers、Marc M. Greenberg

  DOI：10.1021/ja807705z

  日期：2009.2.4

  Base excision repair (BER) enzymes are attractive targets for antiviral and anticancer agents. A number of nucleotides and nucleotide analogues are potent competitive inhibitors of BER glycosylases when they are incorporated into synthetic oligonucleotides. However, these molecules often are not substrates for DNA polymerases, which limits their utility in cells and as potential therapeutic agents. 1'-Cyano-2'-deoxyuridine (CNdU) is a nanomolar competitive inhibitor of uracil DNA glycosylase. In addition, the respective nucleotide triphosphate is accepted as a substrate by the Klenow fragment (exo-) of DNA polymerase I from E. coli. This is the first competitive inhibitor of UDG that is incorporated into DNA by Klenow exo-, a model replicative polymerase. 1'-Cyano-2'-deoxyuridine (CNdU) and related molecules may prove useful as a new family of therapeutic or experimental agents that target DNA repair by using the cells' polymerase(s) to incorporate them into DNA. A potential benefit of such a mechanism is that multiple incorporations can occur for longer DNA molecules leading to amplification of the inhibitory effect beyond that seen here with short DNA duplexes.
• Synthesis and Biological Evaluation of 1′-<i>C</i>-Cyano-Pyrimidine Nucleosides
  作者：Yuichi Yoshimura、Fumitaka Kano、Shuichi Miyazaki、Noriyuki Ashida、Shinji Sakata、Kazuhiro Haraguchi、Yoshiharu Itoh、Hiromichi Tanaka、Tadashi Miyasaka

  DOI：10.1080/07328319608002386

  日期：1996.1

  2'-Deoxy-, 2'-bromo-, and arabine-1'-C-cyano-pyrimidine nucleosides were synthesized from O-2,2'-cyclouridine. Incorporation of cyano group at the anomeric position was achieved by treatment of 1',2'-unsaturated uridine with NBS in the presence of pivalic acid followed by TMS-cyanide and stannic chloride. Antineoplastic and antiviral activities of those compounds are also discussed.