(S)-(((1-(6-aMino-9H-purin-9-yl)propan-2-yloxy)Methyl)phosphoryl)bis(oxy)bis(Methylene) isopropyl dicarbonate fuMarate

• 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: (S)-(((1-(6-aMino-9H-purin-9-yl)propan-2-yloxy)Methyl)phosphoryl)bis(oxy)bis(Methylene) isopropyl dicarbonate fuMarate
• 英文别名: [1-(6-aminopurin-9-yl)propan-2-yloxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(E)-but-2-enedioic acid
• 化学式: C23H34N5O14P
• 分子量: 635.5
• InChiKey: VCMJCVGFSROFHV-WLHGVMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.75
• 重原子数：
  43
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  260
• 氢给体数：
  3
• 氢受体数：
  18

文献信息

• Synthesis Method For Improved Tenofovir Disoproxil Fumarate Using Ion-Exchange Resin And Method For Preparing Oral Dissolving Film Form Using The Same
  申请人：FIRSON

  公开号：US20170354668A1

  公开（公告）日：2017-12-14

  The present invention relates to a synthesis method of preventing the formation of impurities and byproducts in the synthesis of tenofovir disoproxil fumarate (Teno-DF) used as a medicine for hepatitis B and HIV treatment due to its function to promote bioactivities. In the synthesis method of the present invention, an ion-exchange resin (Dowex 50W hydrogen form, sulfonic acidic cation exchange resin) is used to enhance the yield and purity of the compound. The present invention also relates to a method of preparing an oral dissolving film dosage form in the manufacture of a medicine using the tenofovir compound with high purity obtained by the synthesis method of the present invention as an effective ingredient.

  本发明涉及一种合成方法，用于预防在合成用于治疗乙肝和艾滋病的替诺福韦二丙氧基富马酸盐（Teno-DF）的过程中形成杂质和副产物的方法。该化合物因其促进生物活性的功能而被用作药物。在本发明的合成方法中，使用一种离子交换树脂（Dowex 50W氢型，磺酸性阳离子交换树脂）来增强化合物的产率和纯度。本发明还涉及一种制备口溶膜剂型的方法，用于制造药物，使用本发明的合成方法获得的高纯度替诺福韦化合物作为有效成分。
• METHODS FOR IMPROVING PURITY OF TENOFOVIR DISOPROXIL FUMARATE, AND COMPOSITIONS THEREOF
  申请人：AMPAC Fine Chemicals LLC

  公开号：US20200207793A1

  公开（公告）日：2020-07-02

  Methods for producing tenofovir disoproxil fumarate with improved purity are provided. In particular, methods for producing tenofovir disoproxil fumarate with reduced levels of chloromethyl isopropyl carbonate are described. Also described are compositions containing tenofovir disoproxil fumarate with improved purity, and an analysis method that can be used to determine the purity of such compositions with improved accuracy and sensitivity.

  提供了一种生产纯度提高的替诺福韦二丙酰富马酸酯的方法。具体来说，描述了一种生产含有较少氯甲基异丙基碳酸酯的替诺福韦二丙酰富马酸酯的方法。还描述了含有纯度提高的替诺福韦二丙酰富马酸酯的组合物，并提供了一种分析方法，可用于更准确和敏感地确定这种纯度提高的组合物的纯度。
• METHOD OF PRODUCING STABLE CRYSTAL OF 4-OXOQUINOLINE COMPOUND
  申请人：Japan Tobacco Inc.

  公开号：EP3281939A1

  公开（公告）日：2018-02-14

  A method of producing a crystal (crystal form III) of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angels 2θ of 8.54°, 14.02°, 15.68°, 17.06°, 17.24°, 24.16°, 25.74° as measured by X-ray powder diffractometer, wherein the method comprises: dissolving a crystal (crystal form II) of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angles 2θ of 6.56°, 13.20°, 19.86°, 20.84°, 21.22°, 25.22° as measured by X-ray powder diffractometer, in a solvent; and adding a seed crystal (crystal form III) of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, which has an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angles of 2θ of 8.54°, 14.02°, 15.68°, 17.06°, 17.24°, 24.16°, 25.74° as measured by X-ray powder diffractometer, to the solution.

  一种生产6-(3-氯-2-氟苄基)-1-[(S)-1-羟甲基-2-甲基丙基]-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸晶体(晶型III)的方法，该晶体具有X射线粉末衍射图样，衍射角2θ处的特征衍射峰为8.54°、14.02°、15.68°、17.06°、17.24°、24.16°、25.74°，其中该方法包括： 溶解 6-(3-氯-2-氟苄基)-1-[(S)-1-羟甲基-2-甲基丙基]-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸的晶体（晶型 II），该晶体的 X 射线粉末衍射图样在衍射角 2θ 为 6.在 X 射线粉末衍射仪上测量，其特征衍射峰的衍射角 2θ 为 6.56°、13.20°、19.86°、20.84°、21.22°、25.22°、 在溶剂中；以及 在溶剂中加入 6-(3-氯-2-氟苄基)-1-[(S)-1-羟甲基-2-甲基丙基]-7-甲氧基-4-氧代-1,4-二氢喹啉-3-羧酸的籽晶（晶型 III），该籽晶的 X 射线粉末衍射图样在衍射角 2θ 为 8.用 X 射线粉末衍射仪测量，该衍射峰的衍射角为 2θ，即 8.54°、14.02°、15.68°、17.06°、17.24°、24.16°、25.74°。
• Synthesis method for improved tenofovir disoproxil fumarate using ion-exchange resin and method for preparing oral dissolving film form using the same
  申请人：Firson

  公开号：US10155007B2

  公开（公告）日：2018-12-18

  The present invention relates to a synthesis method of preventing the formation of impurities and byproducts in the synthesis of tenofovir disoproxil fumarate (Teno-DF) used as a medicine for hepatitis B and HIV treatment due to its function to promote bioactivities. In the synthesis method of the present invention, an ion-exchange resin (Dowex 50W hydrogen form, sulfonic acidic cation exchange resin) is used to enhance the yield and purity of the compound. The present invention also relates to a method of preparing an oral dissolving film dosage form in the manufacture of a medicine using the tenofovir compound with high purity obtained by the synthesis method of the present invention as an effective ingredient.

  本发明涉及一种在合成富马酸替诺福韦二吡呋酯（Teno-DF）过程中防止杂质和副产物形成的合成方法，富马酸替诺福韦二吡呋酯（Teno-DF）因其具有促进生物活性的功能而被用作乙型肝炎和艾滋病治疗药物。在本发明的合成方法中，使用了一种离子交换树脂（Dowex 50W 氢型磺酸阳离子交换树脂）来提高化合物的产率和纯度。本发明还涉及一种以本发明合成方法获得的高纯度替诺福韦化合物为有效成分的口服溶膜剂型的制备方法。
• Tenofovir granules
  申请人：STEERLIFE INDIA PRIVATE LIMITED

  公开号：US10561614B2

  公开（公告）日：2020-02-18

  The present invention relates to a granular composition comprising essentially Tenofovir, wherein the composition is devoid of an excipient. Tenofovir granules of the present invention are prepared in twin-screw processor such that the content of total impurities in the prepared granules is less than 2.0%.

  本发明涉及一种主要由替诺福韦组成的颗粒组合物，其中该组合物不含赋形剂。本发明的替诺福韦颗粒是在双螺杆处理器中制备的，制备的颗粒中总杂质含量小于 2.0%。