diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate | 441784-88-9

• 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: diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate
• 英文别名: diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]-cyclopropyl}oxy)methylphosphonate；diisopropyl({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate；DiiSopropyl ((1-((2-amino-6-chloro-9H-purin-9-yl)methyl)cyclopropoxy)methyl)phosphonate；6-chloro-9-[[1-[di(propan-2-yloxy)phosphorylmethoxy]cyclopropyl]methyl]purin-2-amine
• CAS: 441784-88-9
• 化学式: C₁₆H₂₅ClN₅O₄P
• 分子量: 417.832
• InChiKey: OXNDWEXNYMMQJE-UHFFFAOYSA-N

物化性质

• 沸点：
  595.5±60.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate 在 palladium on activated charcoal 三甲基溴硅烷 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 25.0~60.0 ℃ 、133.32 Pa 条件下， 反应 84.5h， 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：

  diisopropyl {[1-(hydroxymethyl)cyclopropyl]oxy}methylphosphonate 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate
  参考文献：
  名称：

  [EN] NUCLEOSIDE PHOSPHONATE DERIVATIVES USEFUL IN THE TREATMENT OF HIV INFECTIONS
  [FR] DERIVES DE NUCLEOSIDE PHOSPHONATE UTILES DANS LE TRAITEMENT D'INFECTIONS VIH

  摘要：

  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。

  公开号：

  WO2005079812A1

文献信息

• [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。
• Novel acyclic nucleoside phosphonate derivatives, salts thereof and process for the preparation of the same
  申请人：CHO Dong-Gyu

  公开号：US20100004440A1

  公开（公告）日：2010-01-07

  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（特别是针对乙型肝炎病毒），药学上可接受的盐，立体异构体以及其制备方法。
• J. Med. Chem. 2004, 47, 2864-2869
  作者：

  DOI：——

  日期：——
• US7157448B2
  申请人：——

  公开号：US7157448B2

  公开（公告）日：2007-01-02
• US7605147B2
  申请人：——

  公开号：US7605147B2

  公开（公告）日：2009-10-20