GCD-189 | 444889-02-5

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: GCD-189
• 英文别名: 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine；2-amino-6-(4-methoxyphenylthio)-9-(2-phosphonomethoxyethyl)-purine；2-amino-9-[2-(phosphonomethoxy)ethyl]-6-p-methoxyphenylthiopurine；PP7Uap8wgy；2-[2-amino-6-(4-methoxyphenyl)sulfanylpurin-9-yl]ethoxymethylphosphonic acid
• CAS: 444889-02-5
• 化学式: C₁₅H₁₈N₅O₅PS
• 分子量: 411.378
• InChiKey: MDFHMUJOSKTPIX-UHFFFAOYSA-N

物化性质

• 熔点：
  228-231.5 °C
• 沸点：
  779.7±70.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  171
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  GCD-189 在 N,N'-二环己基-4-吗啉脒 、 磷酸 作用下， 以 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成
  参考文献：
  名称：

  Synthesis and anti-HBV evaluation of mono l-amino acid ester, mono non-steroid anti-inflammation drug carboxylic ester derivatives of acyclonucleoside phosphonates

  摘要：

  A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug (NSAID), carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a "one pot synthesis" method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index (SI) values of 0.48 mu mol/L and 763.72, respectively. (C) 2013 Xiao-Zhong Fu and Yong-Lin Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2013.09.013
• 作为产物：
  描述：

  2-amino-6-(4-methoxyphenylthio)-9-{2-[bis(isopropyloxy)phosphonomethoxy]-ethyl}-purine 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 生成 GCD-189
  参考文献：
  名称：

  EP2511281

  摘要：

  公开号：

文献信息

• PHOSPHORIC ACID/PHOSPHONIC ACID DERIVATIVES AND MEDICINAL USES THEREOF
  申请人：BEIJING MEIBEITA DRUG RES CO., LTD.

  公开号：US20160115186A1

  公开（公告）日：2016-04-28

  The present invention relates to phosphoric acid/phosphonic acid derivatives shown by formula (I), wherein, R 1 or R 2 represents the following structures: (Q1), or (Q2), or (Q3). Q1 represents ester derivatives of L-amino acid, wherein R 3 is alkyl with 1-6 carbon atoms or cycloalkyl, R 4 is H or alkyl with 1-6 carbon atoms; Q2 represents hydroxyl substituted benzodioxane derivatives; Q3 represents hydroxyl substituted benzodioxolane derivatives; R 1 or R 2 is the same or different, but at least one of them is Q2 or Q3; D represents residues of pharmacologically active molecules containing a phosphate/phosphonate group, i.e. formula (II) represents pharmacologically active molecules containing a phosphate/phosphonate group; and when R 1 and R 2 are different, the configuration of the P atom connected to R 1 and R 2 is of R or S type.

  本发明涉及由式（I）所示的磷酸/膦酸衍生物，其中，R1或R2代表以下结构：（Q1），或（Q2），或（Q3）。Q1代表L-氨基酸的酯衍生物，其中R3是具有1-6个碳原子的烷基或环烷基，R4是H或具有1-6个碳原子的烷基；Q2代表羟基取代的苯二噁烷衍生物；Q3代表羟基取代的苯二噁唑烷衍生物；R1或R2相同或不同，但它们中至少有一个是Q2或Q3；D代表含有磷酸/膦酸基团的药理活性分子的残基，即式（II）代表含有磷酸/膦酸基团的药理活性分子；当R1和R2不同时，连接到R1和R2的P原子的构型为R型或S型。
• Acyclic Nucleoside Phosphonate Derivatives and Medical Uses Thereof
  申请人：Zhong Bohua

  公开号：US20120322764A1

  公开（公告）日：2012-12-20

  The present invention relates to an acyclic nucleoside phosphonate derivative and medical uses thereof. Specifically, the present invention relates to an acyclic nucleoside phosphonate derivative of Formula I having strong potency against viruses, such as hepatitis B virus, and low cytotoxicity, or a pharmaceutically acceptable salt, isomer, hydrate or solvate thereof, wherein R 1 is H or methyl; each R 2 is independently —R 3 or —OR 3 , each R 3 is independently C 1 -C 8 alkyl, C 3 -C 8 cycloalkyl. The present invention further relates to a process for preparing the compounds of Formula I, a pharmaceutical composition comprising the compound, and the medical uses of the compound. The acyclic nucleoside phosphonate derivative of the present invention has activity against virus such as hepatitis B virus and good in vivo behavioral traits.

  本发明涉及一种无环核苷酸膦酸酯衍生物及其医药用途。具体而言，本发明涉及一种式I的无环核苷酸膦酸酯衍生物，其对病毒（如乙型肝炎病毒）具有强效力且细胞毒性低，或其药学上可接受的盐、异构体、水合物或溶剂化物，其中R1为H或甲基；每个R2独立地是—R3或—OR3，每个R3独立地是C1-C8烷基、C3-C8环烷基。本发明还涉及制备式I化合物的方法、包含该化合物的制药组合物以及该化合物的医药用途。本发明的无环核苷酸膦酸酯衍生物具有对乙型肝炎病毒等病毒的活性和良好的体内行为特性。
• ACYCLIC NUCLEOSIDE PHOSPHONATE DERIVATIVES AND MEDICINE USES THEREOF
  申请人：Institute Of Pharmacology And Toxicology Academy Of Military Medical Sciences P.L.A. China

  公开号：EP2511281A1

  公开（公告）日：2012-10-17

  An acyclic nucleoside phosphonate derivative and medicine use thereof are provided. In detail, an acyclic nucleoside phosphonate derivative shown in formula I is provided, which has potent antiviral activity (such as hepatitis B virus activity) and less cytotoxicity, and pharmaceutically-acceptable salts, isomers, hydrates or solvates thereof, where, R1 is selected from H or methyl; each R2 is independently selected from -R3 or -OR3; and each R3 is independently selected from C1-C8 alkyl or C3-C8 cycloalkyl. A preparation method of the compounds shown in formula I, a pharmaceutical composition containing the compounds, and a medical application thereof are also provided. The acyclic nucleoside phosphonate derivative is effective for antivirus, such as hepatitis B virus, and is good in vivo behavior attributes.

  提供了一种无环核苷膦酸盐衍生物及其药物用途。具体而言，提供了一种式 I 所示的无环核苷膦酸盐衍生物，该衍生物具有强效抗病毒活性（如乙型肝炎病毒活性）和较低的细胞毒性，并提供了其药学上可接受的盐、异构体、水合物或溶剂，其中，R1 选自 H 或甲基；每个 R2 独立地选自 -R3 或 -OR3；每个 R3 独立地选自 C1-C8 烷基或 C3-C8 环烷基。还提供了式 I 所示化合物的制备方法、含有该化合物的药物组合物及其医疗应用。该无环核苷膦酸盐衍生物对乙型肝炎病毒等抗病毒有效，并具有良好的体内行为特性。
• Antiviral agent for drug-resistant virus
  申请人：MITSUBISHI PHARMA CORPORATION

  公开号：US20030109498A1

  公开（公告）日：2003-06-12

  2-amino-6-arylthiopurinephosphonate used in the antiviral agent of the present invention has no toxicity such as bone marrow cell growth inhibition or mutagenicity, and has a high antiviral activity, oral absorbency and safety. Furthermore, the compound of the present invention is effective for a mutant virus which is known to exhibit resistance to the conventional antiviral agents. Therefore, the present invention can provide a useful antiviral agent which leads to the establishment of a method for treating hepatitis B, which is a medically important object.

  本发明抗病毒剂中使用的 2-氨基-6-芳基硫代嘌呤膦酸盐没有毒性，如骨髓细胞生长抑制或诱变性，并且具有很高的抗病毒活性、口服吸收性和安全性。此外，本发明的化合物对已知对传统抗病毒剂具有抗药性的变异病毒有效。因此，本发明可以提供一种有用的抗病毒剂，从而建立一种治疗乙型肝炎的方法，这在医学上具有重要意义。
• [EN] CRYSTAL OF 2-AMINO-6-(4-METHOXYPHENYLTHIO)-9-[2-(PHOSPHONOMETHOXY)ETHYL]PURINE BIS(2,2,2-TRIFLUOROETHYL) ESTER<br/>[FR] CRISTAL D'ESTER 2-AMINO-6-(4-METHOXYPHENYLTHIO)-9-[2-(PHOSPHONOMETHOXY)ETHYL]PURINE BIS (2,2,2-TRIFLUOROETHYL)
  申请人：MITSUBISHI PHARMA CORP

  公开号：WO2004024743A1

  公开（公告）日：2004-03-25

  ２−アミノ−６−（４−メトキシフェニルチオ）−９−[２−（ホスホノメトキシ）エチル]プリン　ビス（２，２，２−トリフルオロエチル）エステルの新規な結晶、アモルファス及びそれを有効成分とする医薬組成物を提供する。

  2-氨基-6-(4-甲氧基苯硫基)-9-[2-(磷甲氧基)乙基]嘌呤 双(2,2,2-三氟乙基)酯的新晶形、无定形及其作为活性成分的医药组合物。