bis-isopropyloxycarbonylmethyl 9-((R)-2-(phosphonomethoxy)propyl)adenine

• 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: bis-isopropyloxycarbonylmethyl 9-((R)-2-(phosphonomethoxy)propyl)adenine
• 英文别名: tenofovir；bis-POC tenofovir；Tenofovir Disoproxil USP RC A/Tenofovir Disoproxil (S)-Isomer；[1-(6-aminopurin-9-yl)propan-2-yloxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate
• 化学式: C₁₉H₃₀N₅O₁₀P
• 分子量: 519.448
• InChiKey: JFVZFKDSXNQEJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  35
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  185
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  bis-isopropyloxycarbonylmethyl 9-((R)-2-(phosphonomethoxy)propyl)adenine 以 phosphate buffer 为溶剂， 生成 mono-isopropyloxycarbonylmethyl 9-((R)-2-(phosphonomethoxy)propyl)adenine
  参考文献：
  名称：

  溶液中膦酸酯的氧羰基氧甲基前药的降解动力学。

  摘要：

  DOI：

  10.1023/a:1011044804823

文献信息

• An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof
  申请人：Zentiva, k.s.

  公开号：EP2860185A1

  公开（公告）日：2015-04-15

  An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof, comprising following steps: a) alkylation of adenine with (R)-4-methyl-1,3-dioxolan-2-one and isolation of (R)-1-(6-amino-9H-purin-9-yl)propan-2-ol; b) alkylation of (R)-1-(6-amino-9H-purin-9-yl) propan-2-ol with a dialkyl p-toluenesulphonyloxymethylphosphonate or dialkyl halomethylphosphonate to give dialkylester of (R)-9-[2-(phosphonomethoxy)propyl]adenine; c) preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine ((R)-PMPA; Tenofovir) by dealkylation of the phosphonate moiety with a mineral acid under microwave irradiation; d) preparation of Tenofovir disoproxil; e) preparation of the fumarate salt or other pharmaceutically acceptable salt of Tenofovir disoproxil.

  一种改进的Tenofovir disoproxil及其药用盐的制备方法，包括以下步骤：a) 使用(R)-4-甲基-1,3-二氧杂环戊酮烷基化腺嘌呤并分离(R)-1-(6-氨基-9H-嘌呤-9-基)丙醇；b) 使用二烷基对甲苯磺酰氧甲基膦酸酯或二烷基卤代甲基膦酸酯对(R)-1-(6-氨基-9H-嘌呤-9-基)丙醇进行烷基化，得到(R)-9-[2-(磷酸甲氧基)丙基]腺嘌呤的二烷基酯；c) 通过微波辐射下使用矿酸去烷基化磷酸酯部分，制备(R)-9-[2-(磷酸甲氧基)丙基]腺嘌呤((R)-PMPA; Tenofovir)；d) 制备Tenofovir disoproxil；e) 制备Tenofovir disoproxil的富马酸盐或其他药用可接受的盐。
• Blood cell deficiency treatment method
  申请人：——

  公开号：US20030083231A1

  公开（公告）日：2003-05-01

  The invention relates to the use of compounds to treat a number of conditions, such as thrombocytopenia, neutropenia or the delayed effects of radiation therapy. Compounds that can be used in the invention include methyl-2,3,4-trihydroxy-1-O-(7,17-dioxoandrost-5-ene-3&bgr;-yl)-&bgr;-D-glucopyranosiduronate, 16&agr;,3&agr;-dihydroxy-5&agr;-androstan-17-one or 3,7,16,17-tetrahydroxyandrost-5-ene, 3,7,16,17-tetrahydroxyandrost-4-ene,3,7,16,17-tetrahydroxyandrost-1-ene or 3,7,16,17-tetrahydroxyandrostane that can be used in the treatment method.

  该发明涉及使用化合物治疗多种疾病，如血小板减少症、中性粒细胞减少症或放疗延迟效应。可以用于该发明的化合物包括甲基-2,3,4-三羟基-1-O-(7,17-二氧代雄烯-3β-基)-β-D-葡糖吡喃糖醛酸酯、16α,3α-二羟基-5α-雄甾酮-17-酮或3,7,16,17-四羟基雄烷-5-烯、3,7,16,17-四羟基雄烷-4-烯、3,7,16,17-四羟基雄烷-1-烯或3,7,16,17-四羟基雄烷可用于治疗方法中。
• [EN] THE NOVEL TENOFOVIR DISOPROXIL SALT AND THE PREPARATION METHOD THEREOF<br/>[FR] NOUVEAU SEL DE TÉNOFOVIR DISOPROXIL ET PROCÉDÉ POUR LE PRÉPARER
  申请人：CHONG KUN DANG HOLDINGS CORP

  公开号：WO2014035064A1

  公开（公告）日：2014-03-06

  The present invention relates to a novel tenofovir disoproxil aspartate compound. The aforementioned salt compound allows minimal formation of related substances occurring with passage of time, increasing the stability of the formulation by drastically reducing the formation of impurities during storage. Also, the need for a separate study of toxicological effects is eliminated. Moreover, the salt compound of the present invention possesses superior physicochemical properties, with a significant improvement in stability, hygroscopicity, and solubility, thereby allowing it to be used as an active ingredient along with pharmaceutically acceptable carriers for a pharmaceutical composition for the treatment of HIV infection and chronic hepatitis B.

  本发明涉及一种新型替诺福韦二丙氨酸盐化合物。上述盐化合物允许在时间推移时最小化相关物质的形成，通过大幅度减少贮存期间杂质的形成，增加了配方的稳定性。此外，消除了对毒理影响进行单独研究的需求。此外，本发明的盐化合物具有优越的物理化学性质，稳定性、吸湿性和溶解度显著提高，因此可与药学可接受的载体一起用作治疗HIV感染和慢性乙型肝炎的药物组合物的活性成分。
• [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF TENOFOVIR DISOPROXIL AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA PRÉPARATION DE TÉNOFOVIR DISOPROXIL ET DES SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI
  申请人：ZENTIVA KS

  公开号：WO2015051874A1

  公开（公告）日：2015-04-16

  An improved process for the preparation of Tenofovir disoproxil and pharmaceutically acceptable salts thereof, comprising following steps: a) alkylation of adenine with (R)-4-methyl-1,3-dioxolan-2-one and isolation of (R)-1-(6-amino-9H-purin-9-yI)propan-2-ol; b) alkylation of (R)-1-(6-amino-9H-purin-9-yl) propan-2-ol with a dialkyl p-toluenesulphonyloxymethylphosphonate or dialkyl halomethylphosphonate to give dialkylester of (R)-9-[2-(phosphonomethoxy)propyl]adenine; c) preparation of (R)-9-[2-(phosphonomethoxy)propyl]adenine ((R)-PMPA; Tenofovir) by dealkylation of the phosphonate moiety with a mineral acid under microwave irradiation; d) preparation of Tenofovir disoproxil; e) preparation of the fumarate salt or other pharmaceutically acceptable salt of Tenofovir disoproxil.

  一种改进的Tenofovir disoproxil及其药用可接受盐的制备方法，包括以下步骤：a）用（R）-4-甲基-1,3-二氧杂环己-2-酮烷基化腺嘌呤，分离（R）-1-（6-氨基-9H-嘌呤-9-yl）丙-2-醇；b）用二烷基对甲苯磺酰氧甲基膦酸酯或二烷基卤代甲基膦酸酯烷基化（R）-1-（6-氨基-9H-嘌呤-9-yl）丙-2-醇，得到（R）-9- [2-（磷酸甲氧基）丙基]腺嘌呤的二烷基酯；c）通过微波辐射下的矿酸去烷基化磷酸酯基团制备（R）-9- [2-（磷酸甲氧基）丙基]腺嘌呤（（R）-PMPA; Tenofovir）；d）制备Tenofovir disoproxil；e）制备Tenofovir disoproxil的富马酸盐或其他药用可接受盐。
• [EN] NOVEL POLYMORPH OF TENOFOVIR DISOPROXIL MALEATE<br/>[FR] NOUVEAU POLYMORPHE DE MALÉATE DE TÉNOFOVIR DISOPROXIL
  申请人：MYLAN LAB LTD

  公开号：WO2014184802A1

  公开（公告）日：2014-11-20

  The present invention provides a novel crystalline Forms of Tenofovir disoproxil maleate Form-I and Form-II. The present invention further relates to process for the preparation of Tenofovir disoproxil maleate Form-I and Form-II.

  本发明提供了一种新的晶体形式，即替诺福韦二丙氧基琥珀酸盐I型和II型。本发明还涉及制备替诺福韦二丙氧基琥珀酸盐I型和II型的方法。