2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐 | 100708-15-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 中文名称: 2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐
• 中文别名: 替诺福韦杂质118；2-乙酰氧基乙氧甲基膦酸二乙酯
• 英文名称: 2-((diethoxyphosphoryl)methoxy)ethyl acetate
• 英文别名: Diethyl 2-acetoxyethoxymethanephosphonate；(2-acetoxy-ethoxymethyl)-phosphonic acid diethyl ester；(2-Acetoxy-aethoxymethyl)-phosphonsaeure-diaethylester；2-Acetoxy-aethoxymethyl-phosphonsaeure-diaethylester；2-(diethoxyphosphorylmethoxy)ethyl acetate
• CAS: 100708-15-4
• 化学式: C₉H₁₉O₆P
• 分子量: 254.22
• InChiKey: YQYDFGAKKVCPAF-UHFFFAOYSA-N

物化性质

• 沸点：
  123-123.5 °C(Press: 0.5 Torr)
• 密度：
  1.1496 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐 在 Dowex 50x8 (H(+)-form) 四氯化碳 、 三苯基膦 作用下， 以 乙醇 为溶剂， 反应 34.0h， 生成 [(2-氯乙氧基)甲基]膦酸二乙酯
  参考文献：
  名称：

  Holy, Antonin; Rosenberg, Ivan, Collection of Czechoslovak Chemical Communications, 1987, vol. 52, # 11, p. 2801 - 2809

  摘要：

  DOI：
• 作为产物：
  描述：

  2-(氯甲氧基)乙酸乙酯 在 亚磷酸三乙酯 作用下， 以55.4%的产率得到2-((二乙氧基膦酰爪基)甲氧基)乙基醋酸盐
  参考文献：
  名称：

  Method for the preparing \x9b9-12-(Diethoxyphosphonomethoxy)ethyl!adenine

  摘要：

  未受保护的腺嘌呤、6-氯嘌呤、2,6-二氨基嘌呤和2-氨基-6-氯嘌呤已经在一种公开的方法下直接与2-(二乙氧膦酸甲氧基)乙醇偶联，提供了无环膦酸核苷类似物，这些类似物是抗病毒剂如9-\x9b2-(膦酸甲氧基)乙基!腺嘌呤（PMEA）及其结构为公式I的类似物的中间体：##STR1## 其中Z代表N或CH；R.sub.1代表氢、烷基、芳基或芳基烷基；R.sub.2和R.sub.3独立选择自H、OH、卤素、NH.sub.2、C.sub.6 H.sub.5 CH.sub.2 O或R.sub.4 R.sub.5 N，其中R.sub.4和R.sub.5独立选择自烷基、芳基或芳基烷基。

  公开号：

  US05874577A1

文献信息

• Antiviral purine compounds
  申请人：Beecham Group p.l.c.

  公开号：US05247085A1

  公开（公告）日：1993-09-21

  Compounds of formula (I), and pharmaceutically acceptable salts thereof ##STR1## wherein R.sub.1 is hydroxy, amino, chloro or OR.sub.7 wherein R.sub.7 is C.sub.1-6 alkyl, phenyl or phenyl C.sub.1-2 alkyl either of which phenyl moieties may be substituted by one or two substituents selected from halo, C.sub.1-4 alkyl or C.sub.1-4 alkoxy; R.sub.2 is amino or, when R.sub.1 is hydroxy or amino, R.sub.2 may also be hydrogen; R.sub.3 is hydrogen, hydroxymethyl or acyloxymethyl; R.sub.4 is a group of formula: ##STR2## R.sub.5 and R.sub.6 are independently selected from hydrogen, C.sub.1-6 alkyl and optionally substituted phenyl; or R.sub.3 and R.sub.4 together are: ##STR3## wherein R.sub.6 is as defined above; having antiviral activity, to processes for their preparation and their use as pharmaceuticals.

  式(I)的化合物及其药学上可接受的盐，其中R.sub.1是羟基、氨基、氯或OR.sub.7，其中R.sub.7是C.sub.1-6烷基、苯基或苯基C.sub.1-2烷基，其中任一苯基基团可以被选自卤素、C.sub.1-4烷基或C.sub.1-4烷氧基的一个或两个取代基所取代；R.sub.2是氨基，或当R.sub.1是羟基或氨基时，R.sub.2也可以是氢；R.sub.3是氢、羟甲基或酰氧甲基；R.sub.4是下式的基团：##STR2## R.sub.5和R.sub.6独立地选自氢、C.sub.1-6烷基和可选取代的苯基；或R.sub.3和R.sub.4一起是：##STR3## 其中R.sub.6如上定义；具有抗病毒活性，其制备过程及其作为药物的用途。
• Antiviral phosphonomethoxyalkylene purine and pyrimidine derivatives
  申请人：Institute of Organic Chemistry and Biochemistry of the Academy of

  公开号：US05650510A1

  公开（公告）日：1997-07-22

  A series of compounds of Formula I which have anti-tumor activity, and are useful in treating viral infections, their compositions and use. ##STR1## In Formula I B is a purine or pyrimidine base; alk.sub.1 alk.sub.2 and alk.sub.3 are chemical bonds or alkylene groups; Q is hydrogen or hydroxyl; and R.sub.1 -R.sub.4 are hydrogen or alkyl.

  一系列具有抗肿瘤活性的I式化合物，可用于治疗病毒感染，其组成和用途。## STR1 ## 在公式I中，B是嘌呤或嘧啶碱基; alk.sub.1，alk.sub.2和alk.sub.3是化学键或烷基; Q是氢或羟基; R.sub.1-R.sub.4是氢或烷基。
• Synthesis of heterocyclic compounds having phosphorus in the ring
  作者：B. A. Arbuzov、D. Kh. Yarmukhametova

  DOI：10.1007/bf00906562

  日期：1960.10
• Introduction of α-fluorophosphonomethyl ether functionality and its application to the synthesis of fluorinated acyclic phosphonate nucleosides
  作者：Wei Chen、Michael T. Flavin、Robert Filler、Ze-Qi Xu

  DOI：10.1016/s0040-4039(96)02106-5

  日期：1996.12

  Introduction of the alpha-fluorophosphonomethyl ether functionality has been achieved by electrophilic fluorination of the corresponding phosphonomethyl ether carbanion. Coupling of the synthesized 2-[(diethoxyphosphono)fluoromethoxy]ethanol (9) with adenine and 6-chloropurine under Mitsunobu conditions afforded novel fluorinated acyclic phosphonate nucleosides 11a and 11b, respectively. Copyright (C) 1996 Elsevier Science Ltd
• Antitumor effects of guanosine-analog phosphonates identified by molecular modelling
  作者：Anja Schwanke、Caterina Murruzzu、Barbara Zdrazil、Ralf Zuhse、Maja Natek、Monika Höltje、Hans Christian Korting、Hans-Ulrich Reissig、Hans-Dieter Höltje、Monika Schäfer-Korting

  DOI：10.1016/j.ijpharm.2010.06.036

  日期：2010.9

  Aiming to address new drug targets, molecular modelling is gaining increasing importance although the prediction capability of the in silico method is still under debate. For an improved treatment of actinic keratosis and squamous cell carcinoma, inhibitors of human DNA polymerase alpha (pol alpha) are developed by docking nucleoside phosphonate diphosphates into the active site of pol alpha. The most promising prodrugs OxBu and OxHex were then prepared by total synthesis and tested in the squamous cancer cell line SCC25. OxBu and OxHex proved cytotoxic and antiproliferative in the nanomolar concentration range and thus exceeded activity of aphidicolin, the relevant model compound, and 5-fluorouracil, the current standard for the therapy of actinic keratosis. Interestingly, the cytotoxicity in normal human keratinocytes with OxHex was clearly less pronounced and even not detectable with OxBu. Moreover, cytotoxicity of OxBu in particular with the colorectal carcinoma cell line HT29 even surmounted cytotoxicity in SCC25, and other tumor cell lines were influenced, too, by both agents. Taken together, OxBu and OxHex may offer a new approach to cancer therapy, given the agents are sufficiently well tolerated in vivo which is to be suspected beside their chemical structure. (C) 2010 Elsevier B.V. All rights reserved.