双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯 | 186345-40-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: 双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯
• 英文名称: bis(trifluoroethyl) (2-chloroethoxy)methylphosphonate
• 英文别名: [(2-Chloroethoxy)methyl]phosphonic acid bis(2,2,2-trifluoroethyl) ester；2-[2-chloroethoxymethyl(2,2,2-trifluoroethoxy)phosphoryl]oxy-1,1,1-trifluoroethane
• CAS: 186345-40-4
• 化学式: C₇H₁₀ClF₆O₄P
• 分子量: 338.571
• InChiKey: MLQUXJKWKICOHK-UHFFFAOYSA-N

物化性质

• 沸点：
  268.8±40.0 °C(Predicted)
• 密度：
  1.462±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯 在 sodium iodide 作用下， 以 正己烷 、 氯仿 、 丁酮 为溶剂， 生成 bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate
  参考文献：
  名称：

  Phosphonate nucleotide compound

  摘要：

  本发明的2-氨基-6-芳基硫代嘌呤磷酸酯没有骨髓细胞生长抑制和致突变性等毒性，具有较高的抗病毒活性、口服吸收性和安全性。此外，本发明的化合物可以在短过程中生产。因此，本发明可以提供一种能够高效生产的优秀抗病毒剂。

  公开号：

  US20030153534A1
• 作为产物：
  描述：

  三(2,2,2-三氟乙基)亚磷酸酯 、 2-氯乙基氯甲基醚 反应 7.0h， 以100%的产率得到双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯
  参考文献：
  名称：

  无环核苷膦酸酯的单（2、2、2-三氟乙基）酯，单l-氨基酸酯前药的设计，合成和体外评估，作为抗HBV药物

  摘要：

  摘要合成了一系列新型的无环核苷膦酸酯单（2，2，2-三氟乙基）酯，单1-氨基酸酯前药，并在HepG 2 2.2.15细胞中评估了它们的体外抗HBV活性。与阿德福韦酯和阿拉米福韦（MCC-478）相比，化合物1d表现出更强的抗HBV活性和较低的细胞毒性，EC 50和CC 50值分别为0.01μmol/ L和> 8000μmol/ L。

  DOI：

  10.1016/j.cclet.2011.09.005
• 作为试剂：
  描述：

  三(2,2,2-三氟乙基)亚磷酸酯 、 双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯 在 双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯 作用下， 生成 bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate
  参考文献：
  名称：

  2-substituted-5-substituted-1,3-oxathiolanes with antiviral properties

  摘要：

  方法和组合物用于预防或治疗2-取代-5-取代-1,3-噻二氢杂环特征的人类免疫缺陷病毒（HIV）感染。

  公开号：

  US05047407A1

文献信息

• 2-Amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl]purine Bis(2,2,2-trifluoroethyl) Esters as Novel HBV-Specific Antiviral Reagents
  作者：Kouichi Sekiya、Hideaki Takashima、Naoko Ueda、Naohiro Kamiya、Satoshi Yuasa、Yoshiyuki Fujimura、Masaru Ubasawa

  DOI：10.1021/jm020036x

  日期：2002.7.1

  Novel 2-amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) esters were synthesized and evaluated for antihepatitis B virus (HBV) activity in vitro using HB611, HuH-6 cell line, stably transfected with the HBV genome. Among the compounds synthesized, 2-amino-6-phenylthio-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (8), 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl] purine bis(2,2,2-trifluoroethyl) ester (16), 2-amino-6-(3-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (17), and 2-amino-6-(2-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (18) showed considerably high anti-HBV activity, as represented by IC50 values of 0.05, 0.03, 0.04, and 0.08 muM, respectively, and exhibited low cytotoxicity, as represented by CC50 values of more than 1000 muM. It was suggested that these compounds did not have anti-HIV activity, and compound 8 showed only weak anti-HSV-1 activity. An antiviral agent, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA), which was used as a control in the present study, showed moderate anti-HBV activity, as represented by an IC50 value of 0.2 muM. Furthermore, compound 16 was administered orally to mice at a dose of 100 mg/kg in order to examine its gastrointestinal absorbability. Consequently, the main active metabolite was observed in mouse plasma, with especially high concentrations in the liver.
• Synthesis of 2-amino-6-(4-[11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester as a novel potential PET gene reporter probe for HBV and HSV-tk in cancers
  作者：Ji-Quan Wang、Xiangshu Fei、Thomas A. Gardner、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1016/j.bmc.2004.10.007

  日期：2005.1

  Acyclic nucleoside 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (ABE, 1) is a new hepatitis B virus (HBV) specific antiviral reagent and shows high anti-HBV activity. Carbon-11 labeled ABE may serve as a novel reporter probe for positron emission tomography (PET) to image HBV and herpes simplex virus thymidine kinase (HSV-tk) in cancers. The radiolabeling precursors 2-amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (10) and 2-N-Boc protected analogue 2-N-bis(Boc)amino-6-(4-hydroxyphenylthio)9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (12), and the reference standard ABE were synthesized from bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate (5), guanine (6), and 2-amino-6-chloropurine (8). The target radiotracer 2-amino-6-(4-[C-11]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([C-11]ABE, [C-11]1) was prepared by O-[C-11]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [C-11]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields. (C) 2004 Elsevier Ltd. All rights reserved.
• J. Med. Chem. 2002, 45, 3138-3142
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