2-amino-6-chloro-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester | 186345-42-6

• 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-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester
• 英文别名: [2-(2-Amino-6-chloro-purin-9-yl)-ethoxymethyl]-phosphonic acid bis-(2,2,2-trifluoro-ethyl) ester；9-[2-[bis(2,2,2-trifluoroethoxy)phosphorylmethoxy]ethyl]-6-chloropurin-2-amine
• CAS: 186345-42-6
• 化学式: C₁₂H₁₃ClF₆N₅O₄P
• 分子量: 471.683
• InChiKey: CVDCXDKZPDUEIJ-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C
• 沸点：
  542.3±60.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)

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

安全信息

• 储存条件：
  2-8°C，干燥且密封保存。

反应信息

• 作为反应物：
  描述：

  2-amino-6-chloro-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester 在 吡啶 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-[bis(tert-butoxycarbonyl)amino]-6-(4-hydroxyphenylthio)-9-[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
• 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， 以 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 14.0h， 生成 2-amino-6-chloro-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester
  参考文献：
  名称：

  2-Amino-6-arylthio-9-[2-(phosphonomethoxy)ethyl]purine Bis(2,2,2-trifluoroethyl) Esters as Novel HBV-Specific Antiviral Reagents

  摘要：

  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.

  DOI：

  10.1021/jm020036x

文献信息

• Phosphonate nucleotide compound
  申请人：——

  公开号：US20030153534A1

  公开（公告）日：2003-08-14

  The 2-amino-6-arylthiopurinephosphonate of the present invention has no toxicity such as bone marrow cell growth inhibition and mutagenicity, and has a high anti-viral activity, oral absorbency and safety. Furthermore, the compound of the present invention can be produced in a short process. Therefore, the present invention can provide an excellent anti-viral agent which can efficiently be produced.

  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。
• Design, synthesis and in vitro evaluation of mono (2, 2, 2-trifluoroethyl) esters, mono l-amino acid ester prodrugs of acyclic nucleoside phosphonates as anti-HBV agents
  作者：Xiao Zhong Fu、Yu Ou、Jan Xin、Yu She Yang

  DOI：10.1016/j.cclet.2011.09.005

  日期：2011.12

  Abstract A series of novel mono (2, 2, 2-trifluoroethyl) esters, mono l -amino acid ester prodrugs of acyclic nucleoside phosphonates was synthesized and their in vitro anti-HBVactivity was evaluated in HepG 2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil and alamifovir (MCC-478) with EC 50 and CC 50 values of 0.01 μmol/L and

  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。
• US6767900B2
  申请人：——

  公开号：US6767900B2

  公开（公告）日：2004-07-27
• [EN] ANTI-VIRAL AGENTS AND IN-VITRO METHOD FOR THE IDENTIFICATION OF CANDIDATES ABLE TO INHIBIT BINDING OF POLYMERASE TO EPSILON<br/>[FR] AGENTS ANTIVIRAUX ET PROCEDE IN-VITRO D'IDENTIFICATION DE CANDIDATS EMPECHANT LA FIXATION DE LA POLYMERASE A L'EPSILON
  申请人：MITSUBISHI PHARMA CORP

  公开号：WO2003028737A1

  公开（公告）日：2003-04-10

  The object of the present invention is to detect and identify a medicament which inhibits activation of viral polymerase via RNA binding, and also to provide an anti-viral agent using a medicament which inhibits activation of viral polymerase via RNA binding. The present invention provides an anti-viral agent comprising, as an active ingredient, a medicament which inhibits activation of viral polymerase via RNA binding.
• 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.