4-氨基-1-((2R,5S)-2-((叔-丁基二甲基硅烷基氧基)甲基)-1,3-氧硫杂环戊烷-5-基)-5-氟嘧啶-2(1H)-酮 | 1365246-84-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 中文名称: 4-氨基-1-((2R,5S)-2-((叔-丁基二甲基硅烷基氧基)甲基)-1,3-氧硫杂环戊烷-5-基)-5-氟嘧啶-2(1H)-酮
• 英文名称: 4-amino-1-((2R,5S)-2-(((tert-butyldimethylsilyl)oxy)methyl)-1,3-oxathiolan-5-yl)-5-fluoropyrimidin-2(1H)-one
• 英文别名: 4-Amino-1-((2R,5S)-2-((tert-butyldimethylsilyloxy)methyl)-1,3-oxathiolan-5-YL)-5-fluoropyrimidin-2(1H)-one；4-amino-1-[(2R,5S)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-1,3-oxathiolan-5-yl]-5-fluoropyrimidin-2-one
• CAS: 1365246-84-9
• 化学式: C₁₄H₂₄FN₃O₃SSi
• 分子量: 361.513
• InChiKey: PZAVJQRKDBGTSP-WDEREUQCSA-N

物化性质

• 沸点：
  420.9±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于乙酸乙酯、四氢呋喃

计算性质

• 辛醇/水分配系数(LogP)：
  2.57
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-氨基-1-((2R,5S)-2-((叔-丁基二甲基硅烷基氧基)甲基)-1,3-氧硫杂环戊烷-5-基)-5-氟嘧啶-2(1H)-酮 在 吡啶 、 四丁基氟化铵 作用下， 反应 3.0h， 生成 (-)-N4-(4,4'-dimethoxytrityl)-5-fluoro-2',3'-dideoxy-3'-thiacytidine
  参考文献：
  名称：

  Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.

  DOI：

  10.1021/jm201551m
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 、 恩曲他滨 在 咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-氨基-1-((2R,5S)-2-((叔-丁基二甲基硅烷基氧基)甲基)-1,3-氧硫杂环戊烷-5-基)-5-氟嘧啶-2(1H)-酮
  参考文献：
  名称：

  [EN] NRTI THERAPIES
  [FR] THÉRAPIES NRTI

  摘要：

  聚合物前药（POP）材料实现了新的核苷类逆转录酶抑制剂（NRTI）治疗策略。这些材料是核苷类逆转录酶抑制剂的前药，以聚合物的形式存在。适用材料包括聚合物NRTI传递系统的产品，其中包括能够在给药后降解以释放NRTIs或NRTI前药的聚合物材料，这些NRTIs本身能够代谢成母体NRTIs。NRTIs可以选择自替诺福韦（TFV）、恩曲替滨（FTC）、拉米夫定（3TC）和MK-8591（EFdA）。该发明促进了长效（LA）疗程。这些材料的构造可以是注射剂或植入物的形式。

  公开号：

  WO2020128525A1

文献信息

• Design, Synthesis, Antiviral Activity, and Pre-Formulation Development of Poly-<i>L</i>-Arginine-Fatty Acyl Derivatives of Nucleoside Reverse Transcriptase Inhibitors
  作者：Bhanu P. Pemmaraju、Swapnil Malekar、Hitesh K. Agarwal、Rakesh K. Tiwari、Donghoon Oh、Gustavo F. Doncel、David R. Worthen、Keykavous Parang

  DOI：10.1080/15257770.2014.945649

  日期：2015.1.2

  (2015). Design, Synthesis, Antiviral Activity, and Pre-Formulation Development of Poly-L-Arginine-Fatty Acyl Derivatives of Nucleoside Reverse Transcriptase Inhibitors. Nucleosides, Nucleotides & Nucleic Acids: Vol. 34, No. 1, pp. 1-15.

  （2015）。核苷逆转录酶抑制剂的聚-L-精氨酸脂肪酸衍生物的设计，合成，抗病毒活性和预配制开发。核苷，核苷酸和核酸：第1卷。34，第1号，第1-15页。
• [EN] PRODRUG COMPOSITIONS<br/>[FR] COMPOSITIONS DE PROMÉDICAMENTS
  申请人：UNIV LIVERPOOL

  公开号：WO2018178722A1

  公开（公告）日：2018-10-04

  The present invention provides a composition comprising nanoparticles of prodrugs of certain pharmaceutically active agents, wherein the nanoparticles of prodrugs are dispersed within a carrier material. The present invention further provides processes for the making of the same.

  本发明提供一种组合物，其中包括某些药物活性剂的前药纳米粒子，其中前药纳米粒子分散在载体材料中。本发明还提供制造该组合物的方法。
• [EN] NRTI THERAPIES<br/>[FR] THÉRAPIES NRTI
  申请人：UNIV LIVERPOOL

  公开号：WO2020128525A1

  公开（公告）日：2020-06-25

  Polymer-of-prodrug (POP) materials enable new nucleoside reverse transcriptase inhibitor (NRTI) therapy strategies. The materials are prodrugs of NRTIs in the form of polymers. Suitable materials include products which are polymeric NRTI delivery systems comprising polymeric materials which are capable of degradation after administration to release NRTIs or NRTI prodrugs which themselves are capable of metabolism to the parent NRTIs. The NRTIs may optionally be selected from tenofovir (TFV), emtricitabine (FTC), lamivudine (3TC) and MK-8591 (EFdA). The invention facilitates long-acting (LA) regimens. Constructs of the materials may be in the form of injectable compositions or implants.

  聚合物前药（POP）材料实现了新的核苷类逆转录酶抑制剂（NRTI）治疗策略。这些材料是核苷类逆转录酶抑制剂的前药，以聚合物的形式存在。适用材料包括聚合物NRTI传递系统的产品，其中包括能够在给药后降解以释放NRTIs或NRTI前药的聚合物材料，这些NRTIs本身能够代谢成母体NRTIs。NRTIs可以选择自替诺福韦（TFV）、恩曲替滨（FTC）、拉米夫定（3TC）和MK-8591（EFdA）。该发明促进了长效（LA）疗程。这些材料的构造可以是注射剂或植入物的形式。
• Synthesis and Anti-HIV Activities of Glutamate and Peptide Conjugates of Nucleoside Reverse Transcriptase Inhibitors
  作者：Hitesh K. Agarwal、Bhupender S. Chhikara、Megrose Quiterio、Gustavo F. Doncel、Keykavous Parang

  DOI：10.1021/jm201551m

  日期：2012.3.22

  Mono-, di-, and trinucleoside conjugates of glutamate or peptide scaffolds containing nucleoside reverse transcriptase inhibitors were synthesized. Among dinucleoside glutamate ester derivatives, N-myristoylated derivatives showed significantly higher anti-HIV activity than the corresponding N-acetylated conjugates against cell-free virus. Myristoyl-Glu(3TC)-FLT (46, EC50 = 0.3-0.6 mu M) and myristoyl-Glu(FTC)-FLT (47, EC50 = 0.1-0.4 mu M) derivatives were the most active glutamate-dinucleoside conjugates. A trinucleoside glutamate derivative containing AZT, FLT, and 3TC (34, EC50 = 0.9-1.4 mu M) exhibited higher anti-HIV activity than AZT and 3TC against cell-free virus. Compound 34 also exhibited higher anti-HIV activity against multidrug (IC50 = 5.9 nM) and NNRTI (IC50 = 12.9 nM) resistant viruses than parent nucleosides. The physical mixture containing FLT-succinate, AZT, 3TC, and glutamic acid exhibited 115-fold less activity against cell associated virus (EC50 = 91.9 mu M) when compared to 34 (EC50 = 0.8 mu M). Other conjugates showed less or comparable potency to that of the corresponding physical mixtures.