3-(2',3'-dideoxy-ribo-β-L-furanosyl)-6-(9-n-pentyloxynonyl)furo[2,3-d]pyrimidin-2(3H)-one | 1417901-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-(2',3'-dideoxy-ribo-β-L-furanosyl)-6-(9-n-pentyloxynonyl)furo[2,3-d]pyrimidin-2(3H)-one
• 英文别名: 3-(2',3'-dideoxy-ribo-β-L-furanosyl)-6-pentyloxynonylfuro[2,3-d]pyrimidin-2(3H)-one；Cf 3208；Cf3208；3-[(2S,5R)-5-(hydroxymethyl)tetrahydrofuran-2-yl]-6-(9-pentoxynonyl)furo[2,3-d]pyrimidin-2-one；3-[(2S,5R)-5-(hydroxymethyl)oxolan-2-yl]-6-(9-pentoxynonyl)furo[2,3-d]pyrimidin-2-one
• CAS: 1417901-90-6
• 化学式: C₂₅H₄₀N₂O₅
• 分子量: 448.603
• InChiKey: NLLZONVOBYGIQR-PKTZIBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  32
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2',3'-dideoxy-ribo-β-L-furanosyl)-6-(9-n-pentyloxynonyl)furo[2,3-d]pyrimidin-2(3H)-one 在 氨 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以17%的产率得到Cf 3253
  参考文献：
  名称：

  [EN] CONDENSED PYRIMIDINE NUCLEOSIDE ANALOGS AS ANTI -VIRAL AGENTS
  [FR] ANALOGUES DE NUCLÉOSIDES DE PYRIMIDINE CONDENSÉS EN TANT QU'AGENTS ANTIVIRAUX

  摘要：

  已知在嘌呤碱基部分具有6-取代基的3-(2',3'-二去氧-β-L-呋喃核苷基)[2,3-d]嘧啶-2(3H)-酮衍生物具有抗病毒性能，特别是针对天花病毒和麻疹病毒。这些化合物具有非天然的L核糖立体化学结构。

  公开号：

  WO2013007992A1
• 作为产物：
  描述：

  undec-10-yn-1-yl methanesulfonate 在 copper(l) iodide 、 四(三苯基膦)钯 、 sodium hydride 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 43.08h， 生成 3-(2',3'-dideoxy-ribo-β-L-furanosyl)-6-(9-n-pentyloxynonyl)furo[2,3-d]pyrimidin-2(3H)-one
  参考文献：
  名称：

  Novel Antiviral Activity of l-Dideoxy Bicyclic Nucleoside Analogues versus Vaccinia and Measles Viruses in Vitro

  摘要：

  Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with D-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel L-analogues. A structure-activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C9H18-O-n-C5H11. This gave an IC50 of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir. Interestingly, L-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID50 of 7.5 mu M for the lead compound. We propose that L-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.

  DOI：

  10.1021/jm301778x

文献信息

• Novel Nucleoside Analogues as Effective Antiviral Agents for Zika Virus Infections
  作者：Marcella Bassetto、Cecilia M. Cima、Mattia Basso、Martina Salerno、Frank Schwarze、Daniela Friese、Joachim J. Bugert、Andrea Brancale

  DOI：10.3390/molecules25204813

  日期：——

  antiviral agents, we screened against Zika virus replication in vitro in a targeted internal library of small-molecule agents, comprising both nucleoside and non-nucleoside agents. Among the compounds evaluated, novel aryloxyphosphoramidate prodrugs of the nucleosides 2′-C-methyl-adenosine, 2-CMA, and 7-deaza-2′C-methyl-adenosine, 7-DMA, were found to significantly inhibit the virus-induced cytopathic effect

  寨卡病毒以前被认为是一种被忽视的黄病毒，但由于其能够迅速传播并导致严重的神经系统疾病，例如受感染母亲的新生儿小头畸形和成人的格林-巴利综合征，最近已成为公共卫生问题。尽管在确定有效疗法方面付出了大量努力，但仍无法获得特定的抗病毒药物。作为正在进行的确定新抗病毒药物的药物化学研究的一部分，我们在包含核苷和非核苷药物的靶向小分子药物内部文库中针对寨卡病毒的体外复制进行了筛选。在评估的化合物中，核苷 2'-C-甲基-腺苷、2-CMA 和 7-脱氮-2'C-甲基-腺苷、7-DMA 的新型芳氧基磷酰胺前药，发现在多个相关细胞系中显着抑制病毒诱导的细胞病变效应。此外，当与间接抗病毒剂 L-双脱氧双环嘧啶核苷类似物联合应用时，其中一种前药对寨卡病毒表现出协同抗病毒作用，通过靶向宿主途径在体外有效抑制痘苗病毒和麻疹病毒。我们的研究结果为进一步开发寨卡病毒感染的抗病毒疗法奠定了坚实的基础，可能利用结合两种不
• [EN] CONDENSED PYRIMIDINE NUCLEOSIDE ANALOGS AS ANTI -VIRAL AGENTS<br/>[FR] ANALOGUES DE NUCLÉOSIDES DE PYRIMIDINE CONDENSÉS EN TANT QU'AGENTS ANTIVIRAUX
  申请人：UNIV CARDIFF

  公开号：WO2013007992A1

  公开（公告）日：2013-01-17

  3-(2',3'-dideoxy-ribo-β-L-furanosyl)[2,3-d]pyrimidin-2(3H)-one derivatives comprising 6-substitutents on the base moiety are shown to have anti-viral properties, particularly with respect to vaccinia and measles. The compounds have unnatural L ribose stereochemistry.

  已知在嘌呤碱基部分具有6-取代基的3-(2',3'-二去氧-β-L-呋喃核苷基)[2,3-d]嘧啶-2(3H)-酮衍生物具有抗病毒性能，特别是针对天花病毒和麻疹病毒。这些化合物具有非天然的L核糖立体化学结构。
• CONDENSED PYRIMIDINE NUCLEOSIDE ANALOGS AS ANTI-VIRAL AGENTS
  申请人：University College Cardiff Consultants, Ltd.

  公开号：EP2729153B1

  公开（公告）日：2015-09-16
• US8551966B2
  申请人：——

  公开号：US8551966B2

  公开（公告）日：2013-10-08
• Novel Antiviral Activity of <scp>l</scp>-Dideoxy Bicyclic Nucleoside Analogues versus Vaccinia and Measles Viruses in Vitro
  作者：Christopher McGuigan、Karen Hinsinger、Laura Farleigh、Ranjith N. Pathirana、Joachim J. Bugert

  DOI：10.1021/jm301778x

  日期：2013.2.14

  Dideoxy bicyclic pyrimidine nucleoside analogues (ddBCNAs) with D-chirality have previously been described by us to inhibit replication of human cytomegalovirus. We herein report for the first time that activity against vaccinia virus (VACV) was achieved using novel L-analogues. A structure-activity relationship was established: Antiviral activity versus VACV was highest with an ether side chain with an optimum of n-C9H18-O-n-C5H11. This gave an IC50 of 190 nM, a 60-fold enhancement over the FDA-approved antiviral cidofovir. Interestingly, L-ddBCNAs also inhibit wild type measles virus syncytia formation with a TCID50 of 7.5 mu M for the lead compound. We propose that L-ddBCNAs represent significant innovative antiviral candidates versus measles and poxviruses, and we suggest a mechanism of action versus one or more cellular targets that are essential for viral replication.