2-amino-6-chloro-7-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester

• 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: 2-amino-6-chloro-7-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester
• 英文别名: 7-[2-[Bis(2,2,2-trifluoroethoxy)phosphorylmethoxy]ethyl]-6-chloropurin-2-amine
• 化学式: C₁₂H₁₃ClF₆N₅O₄P
• 分子量: 471.683
• InChiKey: WURLYPSZOPIWIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  14

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  2-氨基-6-氯嘌呤	2-Amino-6-chloropurin	10310-21-1	C5H4ClN5	169.573

反应信息

• 作为产物：
  描述：

  双(2,2,2-三氟乙基)[(2-氯乙氧基)甲基]膦酸酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 sodium iodide 作用下， 生成 2-amino-6-chloro-7-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2004.10.007

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.