1-(2-deoxy-2-fluoro-3-O-mesyl-5-O-triphenylmethyl-β-D-arabinofuranosyl)thymine | 128114-98-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(2-deoxy-2-fluoro-3-O-mesyl-5-O-triphenylmethyl-β-D-arabinofuranosyl)thymine
• 英文别名: 1-(2-deoxy-2-fluoro-3-O-mesyl-5-O-trityl-β-D-arabinofuranosyl)thymine；1-(2-Deoxy-2-fluoro-3-O-mesyl-5-O-trityl-beta-D-arabinofuranosyl)thymine；[(2R,3R,4S,5R)-4-fluoro-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2-(trityloxymethyl)oxolan-3-yl] methanesulfonate
• CAS: 128114-98-7
• 化学式: C₃₀H₂₉FN₂O₇S
• 分子量: 580.634
• InChiKey: UAARHHOLHGXMMT-IYOUEGCASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(2-deoxy-2-fluoro-3-O-mesyl-5-O-triphenylmethyl-β-D-arabinofuranosyl)thymine 在 sodium hydroxide 、 溶剂黄146 作用下， 以 乙醇 、 水 为溶剂， 反应 3.5h， 生成 2,3'-anhydro-1-(2-deoxy-2-fluoro-β-D-lyxofuranosyl)thymine
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogs of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC)

  摘要：

  1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.

  DOI：

  10.1021/jm00170a016
• 作为产物：
  描述：

  2'-氟-5-甲基阿拉伯糖基尿嘧啶 在 吡啶 作用下， 反应 3.5h， 生成 1-(2-deoxy-2-fluoro-3-O-mesyl-5-O-triphenylmethyl-β-D-arabinofuranosyl)thymine
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 2'-"up"-fluoro analogs of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC)

  摘要：

  1-(3-Azido-2,3-dideoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-beta-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)thymine (1, FMAU) and 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC) in the hope that introduction of a 2-"up"-fluoro substituent might potentiate the anti-HIV activity of AZT and DDC. FMAU (1) was converted in three steps into 2,3'-anhydro-1-(2-fluoro-2-deoxy-5-O-trityl-beta-D-lyxofuranosyl)thymine (4), which when treated with NaN3 followed by detritylation afforded 6. F-DDC was prepared by two methods. Tritylation of FIAC followed by treatment of the product with thiocarbonyldimidazole afforded the 5'-O-trityl-3'-O-(imidazolyl)thiocarbonyl nucleoside 9. Upon radical reduction of 9 with Bu3SnH and AIBN, 5'-O-trityl-DDC 10 was obtained. Compound 10 was detritylated to give 12, which (when obtained by this procedure) resisted crystallization, but the diacetate 12' was obtained in crystalline form. Alternatively, FAC (14) was converted into N4,O5'-dibenzoyl derivative 15, which was treated with thiocarbonyldiimidazole. Reduction of 16 with Bu3SnH/AIBN followed by debenzoylation afforded 12, which was obtained in crystalline form. F-AZT did not exhibit any significant activity against the human immunodeficiency virus (HIV) in vitro. F-DDC, however, showed activity against HIV-1, but the therapeutic index is much inferior to that of AZT.

  DOI：

  10.1021/jm00170a016

文献信息

• Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
  申请人：——

  公开号：US20030087873A1

  公开（公告）日：2003-05-08

  The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  该公开的发明涉及一种用于治疗Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括甲型和乙型流感）或Paramyxoviridae（包括RSV）感染或与异常细胞增殖有关的病况的组合物和方法，适用于宿主，包括动物，尤其是人类，使用通用式（I）-（XXIII）的核苷或其药学上可接受的盐或前药。该发明还提供了一种有效的过程，用于量化病毒载量，特别是BVDV、HCV或西尼罗河病毒载量，使用实时聚合酶链反应（RT-PCR）。此外，该发明揭示了可以与样本中存在的病毒数量成比例发光的探针分子。
• Fluorinated sugar analogs of potential anti-HIV-1 nucleosides
  作者：Jai Tung Huang、Ling Ching Chen、Liben Wang、Moon Hwan Kim、James A. Warshaw、Donald Armstrong、Qing Yu Zhu、Ting Chao Chou、Kyoichi A. Watanabe

  DOI：10.1021/jm00109a017

  日期：1991.5

  3'-dideoxy-5-methyluridine (31), and 2'3'-dideoxy-2' -fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents

  为了获得具有优于AZT，FLT或D4T的治疗指数的药物，合成了抗HIV-1核苷的几种类似物。这些包括2'，3'-dideoxy-2'，3'-difluoro-5-methyluridine（13），其阿拉伯糖类似物19，arab-5--5-甲基胞嘧啶类似物21、3'-脱氧2'，3'-二氢-2'-氟胸苷（25），3'-叠氮基2'，3'-二脱氧基2'-氟-5-甲基尿苷（29），2'-叠氮基3'-氟-2'，3'-双脱氧-5-甲基尿苷（31）和2'3'-二脱氧-2'-氟-5-甲基尿苷（37）。对这些新核苷在体外针对HIV和猫TLV的活性进行了筛选。没有一种化合物显示出明显的活性。有趣的是，活性抗HIV核苷的糖部分有这么小的修饰（即
• Modified nucleosides for the treatment of viral infections and abnormal cellullar proliferation
  申请人：Stuyver Lieven

  公开号：US20110269707A1

  公开（公告）日：2011-11-03

  The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  本公开发明涉及一种用于治疗Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括甲型和乙型流感）或Paramyxoviridae（包括RSV）感染或与异常细胞增殖相关的条件的组合物和方法，适用于宿主，包括动物，特别是人类，使用通式（I）-（XXIII）的核苷或其药学上可接受的盐或前药。本发明还提供了一种有效的过程，用于定量病毒载量，特别是BVDV、HCV或西尼罗河病毒载量，在宿主中使用实时聚合酶链反应（“RT-PCR”）。此外，本发明还揭示了探针分子，可以与样品中存在的病毒数量成比例地发出荧光。
• MODIFIED NUCLEOSIDES FOR THE TREATMENT OF VIRAL INFECTIONS AND ABNORMAL CELLULAR PROLIFERATION
  申请人：GILEAD SCIENCES, INC.

  公开号：US20140057863A1

  公开（公告）日：2014-02-27

  The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

  本公开发明涉及一种用于治疗Flaviviridae（包括BVDV和HCV）、Orthomyxoviridae（包括甲型和乙型流感病毒）或Paramyxoviridae（包括RSV）感染或与异常细胞增殖相关的条件的组合物和方法，适用于宿主，包括动物，特别是人类，使用一种核苷酸的一般式（I）-（XXIII）或其药学上可接受的盐或前药。本发明还提供了一种有效的过程，用于定量病毒载量，特别是BVDV、HCV或West Nile病毒载量，在宿主中使用实时聚合酶链反应（“RT-PCR”）。此外，本发明还揭示了可以与样品中存在的病毒数量成比例发光的探针分子。
• WATANABE, KYOICHI A.;HARADA, KAZUHO;ZEIDLER, JOANNA;MATULIC-ADAMIC, JASEN+, J. MED. CHEM., 33,(1990) N, C. 2145-2150
  作者：WATANABE, KYOICHI A.、HARADA, KAZUHO、ZEIDLER, JOANNA、MATULIC-ADAMIC, JASEN+

  DOI：——

  日期：——