[[[1-[[(甲基磺酰基)氧基]甲基]环丙基]氧基]甲基]膦酸二异丙酯 | 441784-86-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 中文名称: [[[1-[[(甲基磺酰基)氧基]甲基]环丙基]氧基]甲基]膦酸二异丙酯
• 英文名称: {1-[(diisopropylphosphoryl)methoxy]cyclopropyl}methyl methanesulfonate
• 英文别名: {1-[(diisopropoxyphosphoryl)methoxy]cyclopropyl}methyl methane-sulfonate；{1-[(diisopropoxyphosphoryl)methoxy]cyclopropyl}methylmethanesulfonate；[[[1-[[(Methylsulfonyl)oxy]methyl]cyclopropyl]oxy]methyl]phosphonic acid bis(1-methylethyl) ester；[1-[di(propan-2-yloxy)phosphorylmethoxy]cyclopropyl]methyl methanesulfonate
• CAS: 441784-86-7
• 化学式: C₁₂H₂₅O₇PS
• 分子量: 344.366
• InChiKey: UUPWOYCMTIVVSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [[[1-[[(甲基磺酰基)氧基]甲基]环丙基]氧基]甲基]膦酸二异丙酯 在 palladium on activated charcoal 三甲基溴硅烷 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0~80.0 ℃ 、133.32 Pa 条件下， 反应 89.0h， 生成 LB-80380
  参考文献：
  名称：

  A Novel Class of Phosphonate Nucleosides. 9-[(1-Phosphonomethoxycyclopropyl)methyl]guanine as a Potent and Selective Anti-HBV Agent

  摘要：

  9-[1-(Phosphonomethoxycyclopropyl)methyl]guanine (PMCG, 1), representative of a novel class of phosphonate nucleosides, blocks HBV replication with excellent potency (EC50 = 0.5 muM) in a primary culture of HepG2 2.2.15 cells. It exhibits no significant cytotoxicity in several human cell lines up to 1.0 mM. It does not inhibit replication of human immunodeficiency virus (HIV-1) or herpes simplex virus (HSV-1) at 30 muM. Many purine base analogues of 1 also exhibit inhibitory activity against HBV, but at 30 muM, pyrimidine analogues do not. 1 is 4 times more potent than 9- [2-(phosphonomethoxy)ethyl] adenine (PMEA), which was used as a positive control (EC50 = 2.0 muM). The characteristic cyclopropyl moiety at the 2'-position of 1 was prepared by titanium-mediated Kulinkovich cyclopropanation. 1 was modified to give the orally available drug candidate, PMCDG Dipivoxil (2). Compound 2 exhibited excellent efficacy when administered at 5 mg per kg per day in a study with woodchucks infected with woodchuck hepatitis B virus (WHBV). Drug candidate 2 has successfully completed phase I clinical trials and is currently undergoing phase II clinical studies for evaluation of efficacy.

  DOI：

  10.1021/jm0305265
• 作为产物：
  描述：

  溴甲基膦酸二异丙酯 在 氟化铵 、 三乙胺 、 lithium iodide 、 lithium tert-butoxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 [[[1-[[(甲基磺酰基)氧基]甲基]环丙基]氧基]甲基]膦酸二异丙酯
  参考文献：
  名称：

  A Novel Class of Phosphonate Nucleosides. 9-[(1-Phosphonomethoxycyclopropyl)methyl]guanine as a Potent and Selective Anti-HBV Agent

  摘要：

  9-[1-(Phosphonomethoxycyclopropyl)methyl]guanine (PMCG, 1), representative of a novel class of phosphonate nucleosides, blocks HBV replication with excellent potency (EC50 = 0.5 muM) in a primary culture of HepG2 2.2.15 cells. It exhibits no significant cytotoxicity in several human cell lines up to 1.0 mM. It does not inhibit replication of human immunodeficiency virus (HIV-1) or herpes simplex virus (HSV-1) at 30 muM. Many purine base analogues of 1 also exhibit inhibitory activity against HBV, but at 30 muM, pyrimidine analogues do not. 1 is 4 times more potent than 9- [2-(phosphonomethoxy)ethyl] adenine (PMEA), which was used as a positive control (EC50 = 2.0 muM). The characteristic cyclopropyl moiety at the 2'-position of 1 was prepared by titanium-mediated Kulinkovich cyclopropanation. 1 was modified to give the orally available drug candidate, PMCDG Dipivoxil (2). Compound 2 exhibited excellent efficacy when administered at 5 mg per kg per day in a study with woodchucks infected with woodchuck hepatitis B virus (WHBV). Drug candidate 2 has successfully completed phase I clinical trials and is currently undergoing phase II clinical studies for evaluation of efficacy.

  DOI：

  10.1021/jm0305265

文献信息

• [EN] NUCLEOSIDE PHOSPHONATE DERIVATIVES USEFUL IN THE TREATMENT OF HIV INFECTIONS<br/>[FR] DERIVES DE NUCLEOSIDE PHOSPHONATE UTILES DANS LE TRAITEMENT D'INFECTIONS VIH
  申请人：ANADYS PHARMACEUTICALS INC

  公开号：WO2005079812A1

  公开（公告）日：2005-09-01

  The present invention relates to a method of treating HIV infections by administering a nucleoside phosphonate derivative represented by formula (I).

  本发明涉及通过给予由式(I)表示的核苷酸膦酸衍生物来治疗HIV感染的方法。
• [EN] NEW PROCESS FOR PREPARING DIISOPROPYL ((1-((2-AMINO-6-CHLORO-9H-PURIN-9-YL)METHYL)CYCLOPROPYL)OXY)METHYLPHOSPHONATE<br/>[FR] NOUVEAU PROCEDE DE PREPARATION DE DIISOPROPYL((1-((2-AMINO-6-CHLORO-9H-PURIN-9-YL)METHYL)CYCLOPROPYL)OXY)METHYLPHOSPHONATE
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2005058926A1

  公开（公告）日：2005-06-30

  The present invention relates to a new process for preparing the compound of formula (1) which is important intermediate for preparation of nucleoside analog of the compound of formula (2) effective as antiviral agent, in particular hepatitis B viral agent.

  本发明涉及一种用于制备化合物（1）的新工艺，该化合物是制备化合物（2）的重要中间体，化合物（2）是一种作为抗病毒剂，特别是肝炎B病毒制剂的核苷类似物的有效中间体。
• [EN] NEW PROCESS FOR PREPARING DIISOPROPYL ((1-((2-AMINO-6-HALO-9H-PURIN-9-YL)METHYL)CYCLOPROPYL)OXY)METHYLPHOSPHONATE<br/>[FR] NOUVEAU PROCEDE DE PREPARATION DE DIISOPROPYL ((1-((2-AMINO-6-HALO-9H-PURIN-9-YL)METHYL)CYCLOPROPYLE)OXY)METHYLPHOSPHONATE
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2005058925A1

  公开（公告）日：2005-06-30

  The present invention relates to a new process for preparing the compound of formula (1) which is important intermediate for preparation of nucleoside analog of the compound of formula (2) effective as antiviral agent, in particular hepatitis B viral agent.

  本发明涉及一种制备式（1）化合物的新工艺，该化合物是制备式（2）化合物核苷类似物的重要中间体，该化合物是一种抗病毒制剂，特别是对乙型肝炎病毒制剂有效。
• Nucleoside phosphonate derivatives useful in the treatment of HIV infections
  申请人：Averett R. Devron

  公开号：US20060052346A1

  公开（公告）日：2006-03-09

  The present invention relates to a method of treating HIV infections by administering a nucleoside phosphonate derivative represented by formula (1).

  本发明涉及通过给予由式（1）表示的核苷酸膦酸衍生物治疗HIV感染的方法。
• Novel acyclic nucleoside phosphonate derivatives, salts thereof and process for the preparation of the same
  申请人：——

  公开号：US20040063668A1

  公开（公告）日：2004-04-01

  The present invention relates to an acyclic nucleoside phosphonate derivative which is useful as an antiviral agent (particularly, against hepatitis B virus), pharmaceutically acceptable salts, stereoisomers, and a process for the preparation thereof.

  本发明涉及一种无环核苷酸膦酸酯衍生物，其可用作抗病毒剂（特别是对乙型肝炎病毒），药学上可接受的盐，立体异构体以及其制备方法。