1-(adenin-9-yl)-3-O-(diisopropylphosphonomethyl)-L-threose | 849778-81-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 1-(adenin-9-yl)-3-O-(diisopropylphosphonomethyl)-L-threose
• 英文别名: (2R,3R,4S)-2-(6-aminopurin-9-yl)-4-[di(propan-2-yloxy)phosphorylmethoxy]oxolan-3-ol
• CAS: 849778-81-0
• 化学式: C₁₆H₂₆N₅O₆P
• 分子量: 415.386
• InChiKey: SRBUTLKTRXWRSG-NORZTCDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(adenin-9-yl)-3-O-(diisopropylphosphonomethyl)-L-threose 在 4-二甲氨基吡啶 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 18.0h， 生成 1-(adenin-9-yl)-2-deoxy-3-O-(diisopropylphosphonomethyl)-L-threose
  参考文献：
  名称：

  脱氧苏糖基膦酸酯核苷作为选择性抗 HIV 药物

  摘要：

  在一系列具有 l-苏糖和 l-2-脱氧苏糖糖部分的八种新膦酸核苷中，鉴定出两种新化合物（PMDTA 和 PMDTT），它们显示出有效的抗 HIV-1 (HIV-2) 活性 [EC50 = 2.53 microM (PMDTA) 和 6.59 microM (PMDTT)]，而在测试的最高浓度下未观察到细胞毒性 [CC50 > 316 microM (PMDTA) 和 > 343 microM (PMDTT)]。PMDTA 掺入 DNA 的动力学（使用 PMDTA 的二磷酸盐作为底物，HIV-1 逆转录酶作为催化剂）与观察到的 dATP 动力学相似，而 PMDTA 的二磷酸盐是 DNA 聚合酶 α 的非常差的底物。掺入的 PMDTA 非常适合 HIV-1 逆转录酶的活性位点口袋。

  DOI：

  10.1021/ja043045z
• 作为产物：
  描述：

  1'α-(N6-benzoyladenin-9-yl)-2'-O-benzoyl-3'-O-diisopropyl-phosphonomethyl-L-threose 在 氨 作用下， 以 甲醇 为溶剂， 以84%的产率得到1-(adenin-9-yl)-3-O-(diisopropylphosphonomethyl)-L-threose
  参考文献：
  名称：

  脱氧苏糖基膦酸酯核苷作为选择性抗 HIV 药物

  摘要：

  在一系列具有 l-苏糖和 l-2-脱氧苏糖糖部分的八种新膦酸核苷中，鉴定出两种新化合物（PMDTA 和 PMDTT），它们显示出有效的抗 HIV-1 (HIV-2) 活性 [EC50 = 2.53 microM (PMDTA) 和 6.59 microM (PMDTT)]，而在测试的最高浓度下未观察到细胞毒性 [CC50 > 316 microM (PMDTA) 和 > 343 microM (PMDTT)]。PMDTA 掺入 DNA 的动力学（使用 PMDTA 的二磷酸盐作为底物，HIV-1 逆转录酶作为催化剂）与观察到的 dATP 动力学相似，而 PMDTA 的二磷酸盐是 DNA 聚合酶 α 的非常差的底物。掺入的 PMDTA 非常适合 HIV-1 逆转录酶的活性位点口袋。

  DOI：

  10.1021/ja043045z

文献信息

• Phosponate nucleosides useful as active ingredients in pharmaceutical compositions for the treatment of viral infections, and intermediates for their production
  申请人：Herdewijn Piet

  公开号：US20070185062A1

  公开（公告）日：2007-08-09

  The present invention relates to novel phosponate nucleosides, more specifically to novel phosponalkoxy substituted nucleosides. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

  本发明涉及新型磷酸酯核苷，更具体地涉及新型磷酸酯烷氧基取代核苷。本发明还涉及具有抑制HIV（人类免疫缺陷病毒）复制作用的化合物，以及具有抗其他病毒活性的化合物。本发明还涉及制备所有这些化合物的方法和包含它们的制药组合物。本发明还涉及将所述化合物用作药物以及制造有用于治疗HIV感染患者的药物，以及用于治疗其他病毒、逆转录病毒或慢病毒感染和治疗患有FIV、病毒、逆转录病毒或慢病毒感染的动物的药物的用途。
• PHOSPHONATE NUCLEOSIDES USEFUL AS ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS, AND INTERMEDIATES FOR THEIR PRODUCTION
  申请人：Herdewijn Piet

  公开号：US20120108531A1

  公开（公告）日：2012-05-03

  Disclosed herein are novel phosphonate nucleosides and thiophosphonate nucleosides comprising a phosphonalkoxy-substituted or phosphonothioalkyl-substituted five-membered, saturated or unsaturated, oxygen-containing or sulfur-containing ring coupled to a heterocyclic nucleobase such as a pyrimidine or purine base. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.

  本文披露了一种新型磷酸酯核苷和硫代磷酸酯核苷，包括一个磷酸烷氧基取代或磷酸硫烷基取代的五元环，该环饱和或不饱和，含氧或含硫，与杂环核苷碱（如嘧啶或嘌呤碱基）结合。本发明还涉及具有HIV（人类免疫缺陷病毒）复制抑制性质的化合物，以及具有抗其他病毒活性的化合物。本发明还涉及制备所有这些化合物的方法和包含它们的药物组合物。本发明还涉及将所述化合物用作药物，并制造一种有用于治疗HIV感染患者以及治疗其他病毒、逆转录病毒或慢病毒感染和治疗患有FIV、病毒、逆转录病毒或慢病毒感染的动物的药物的药物。
• Phosphonomethyl Oligonucleotides as Backbone-Modified Artificial Genetic Polymers
  作者：Chao Liu、Christopher Cozens、Faten Jaziri、Jef Rozenski、Amandine Maréchal、Shrinivas Dumbre、Valérie Pezo、Philippe Marlière、Vitor B. Pinheiro、Elisabetta Groaz、Piet Herdewijn

  DOI：10.1021/jacs.8b03447

  日期：2018.5.30

  Although several synthetic or xenobiotic nucleic acids (XNAs) have been shown to be viable genetic materials in vitro, major hurdles remain for their in vivo applications, particularly orthogonality. The availability of XNAs that do not interact with natural nucleic acids and are not affected by natural DNA processing enzymes, as well as specialized XNA processing enzymes that do not interact with natural nucleic acids, is essential. Here, we report 3'-2' phosphonomethylthreosyl nucleic acid (tPhoNA) as a novel XNA genetic material and a prime candidate for in vivo XNA applications. We established routes for the chemical synthesis of phosphonate nucleic acids and phosphorylated monomeric building blocks, and we demonstrated that DNA duplexes were destabilized upon replacement with tPhoNA. We engineered a novel tPhoNA synthetase enzyme and, with a previously reported XNA reverse transcriptase, demonstrated that tPhoNA is a viable genetic material (with an aggregate error rate of approximately 17 X 10(-3) per base) compatible with the isolation of functional XNAs. In vivo experiments to test tPhoNA orthogonality showed that the E. coli cellular machinery had only very limited potential to access genetic information in tPhoNA. Our work is the first report of a synthetic genetic material modified in both sugar and phosphate backbone moieties and represents a significant advance in biorthogonality toward the introduction of XNA systems in vivo.
• [EN] PHOSPONATE NUCLEOSIDES USEFUL AS ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS, AND INTERMEDIATES FOR THEIR PRODUCTION<br/>[FR] NUCLEOSIDES PHOSPHONATES UTILES EN TANT QUE PRINCIPES ACTIFS DANS DES COMPOSITIONS PHARMACEUTIQUES POUR LE TRAITEMENT D'INFECTIONS VIRALES, ET INTERMEDIAIRES POUR LEUR PRODUCTION
  申请人：LEUVEN K U RES & DEV

  公开号：WO2005085268A3

  公开（公告）日：2005-10-13
• PHOSPONATE NUCLEOSIDES USEFUL AS ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS, AND INTERMEDIATES FOR THEIR PRODUCTION
  申请人：K.U.Leuven Research & Development

  公开号：EP1720890B1

  公开（公告）日：2015-05-20