({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphinic acid | 919512-65-5

• 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: ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphinic acid
• 英文别名: (R)-9-[2-(hydroxyphosphinylmethoxy)propyl]adenine；[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphinic acid
• CAS: 919512-65-5
• 化学式: C₉H₁₄N₅O₃P
• 分子量: 271.216
• InChiKey: HCJJLBXMPXTCDB-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphinic acid 在 吡啶 、 N,O-双三甲硅基乙酰胺 作用下， 反应 1.5h， 生成 泰诺福韦
  参考文献：
  名称：

  Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication

  摘要：

  9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the alpha-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 degrees C in several media. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.06.034
• 作为产物：
  描述：

  替诺福韦二乙酯 在 lithium aluminium tetrahydride 、 三甲基氯硅烷 、 双氧水 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 ({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphinic acid
  参考文献：
  名称：

  9- [2-（膦酰基甲氧基）乙基]腺嘌呤和（R）-9- [2-（膦酰基甲氧基）丙基]腺嘌呤的新型α-硼烷核苷酸类似物的合成，体外抗病毒评价和稳定性研究。

  摘要：

  我们在这里描述9- [2-（硼基膦酰基甲氧基）乙基]腺嘌呤（6a）和（R）-9- [2-（硼基膦酰基甲氧基）丙基]腺嘌呤（6b）的合成，其中第一个α-硼烷膦酸酯核苷为硼烷（BH3）基团取代了α-膦酸酯部分的一个非桥接氧原子。评估了H-次膦酸盐5a和5b以及α-硼烷膦酸盐6a和6b的抗人免疫缺陷病毒（HIV）感染细胞以及一系列DNA或RNA病毒的体外活性。化合物5a，5b，6a和6b在体外和细胞毒性方面均未显示出明显的抗病毒活性。为了测量目标化合物6a和6b的化学和酶稳定性，在几种介质中于37摄氏度研究了衍生物5a，5b，6a，6b和标准化合物的分解动力学数据。

  DOI：

  10.1021/jm060030y

文献信息

• [EN] A PROCESS FOR THE PREPARATION OF (R)-9-[2-(PHOSPHONOMETH-OXY)PROPYL]ADENINE (PMPA)<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (R)-9-[2-(PHOSPHONOMETH-OXY)PROPYL]ADENINE (PMPA)
  申请人：ITHEMBA PHARMACEUTICALS PROPRIETARY LTD

  公开号：WO2014033688A1

  公开（公告）日：2014-03-06

  This invention relates to a process for the preparation of (R)-9-[2- (phosphonometh-oxy)propyl]adenine (PMPA). This invention also relates to the preparation of Tenofovir disoproxil fumarate (TDF), a compound which can be produced from PMPA. The claimed process comprises reacting compound (6) with compound (7) in presence of 2,2,6,6- tetramethylpiperidinylmagnesium to compound (2), which is hydrolysed to (3).

  这项发明涉及一种制备(R)-9-[2-(磷酸甲氧基)丙基]腺嘌呤（PMPA）的过程。这项发明还涉及Tenofovir disoproxil fumarate（TDF）的制备，这是一种可以从PMPA生产的化合物。所述的过程包括在2,2,6,6-四甲基哌啶基镁的存在下，将化合物（6）与化合物（7）反应，得到化合物（2），然后水解为（3）。
• NOVEL NUCLEOTIDE ANALOGUES AS PRECUSOR MOLECULES FOR ANTIVIRALS
  申请人：Canard Bruno

  公开号：US20100099869A1

  公开（公告）日：2010-04-22

  This invention relates to a purine or pyrimidine phosphonate compound of formula (I) or pharmaceutically acceptable salt thereof; wherein B, X, and R 1 -R 3 are as defined in classes and subclasses herein. These compounds may be used as antiviral precursors. The invention also relates to therapeutic compositions of these compounds and their use for the preparation of a medication for testing and/or preventing a viral infection in a patient. The invention also provides methods for making these compounds. In particular, the invention provides an H-phosphinate precursor intermediate of formula (II) wherein B is a purine or pyrimidine base as defined herein and R 1 is selected from the group comprising a hydrogen atom, and a methyl, ethyl, hydroxymethyl, hydroxyethyl and C 1-6 haloalkyl group.

  本发明涉及一种嘌呤或嘧啶磷酸酯化合物(I)或其药学上可接受的盐；其中B、X和R1-R3的定义如本文中的类和子类所述。这些化合物可以用作抗病毒前体。本发明还涉及这些化合物的治疗组合物及其用于制备用于测试和/或预防患者病毒感染的药物。本发明还提供制备这些化合物的方法。特别是，本发明提供了一种公式(II)的H-磷酸酯前体中间体，其中B是如本文所述的嘌呤或嘧啶碱基，R1选自包括氢原子，甲基，乙基，羟甲基，羟乙基和C1-6卤代烷基的群体。
• Prodrugs of phosphonate nucleotide analogues and methods for selecting and making same
  申请人：GILEAD SCIENCES, INC.

  公开号：EP2682397A1

  公开（公告）日：2014-01-08

  An improved method for the use of magnesium alkoxide for the preparation of starting materials and compounds for use herein is provided. The method is useful for preparing compounds of structure (5a) having substituent groups as defined herein which compounds can be used in antiviral therapy and prophylaxis.

  本文提供了一种使用氧化镁制备起始原料和化合物的改进方法。该方法可用于制备结构 (5a) 的化合物 该化合物可用于抗病毒治疗和预防。
• WO2008/56264
  申请人：——

  公开号：——

  公开（公告）日：——
• (R)-9-[2-(Hydroxyphosphinylmethoxy)propyl]adenine as the precursor molecule for antivirals
  作者：Loic Roux、Bruno Canard、Karine Alvarez

  DOI：10.1016/j.tetlet.2014.05.061

  日期：2014.7

  The biological importance and practical significance of phosphonates have been a major driving force for antiviral research in the past two decades. We describe in this Letter the potential of the H-phosphinate derivative (R)-9-[2-(hydroxyphosphinylmethoxy)propyl]adenine as the versatile synthetic intermediate in the preparation of N-alkylphosphonamidate and alkylphosphonate series. (C) 2014 Elsevier Ltd. All rights reserved.