diisopropyl ({1-[(2-amino-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate | 693788-86-2

• 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-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate
• 英文别名: DiiSopropyl ((1-((2-amino-9H-purin-9-yl)methyl)cyclopropoxy)methyl)phosphonate；9-[[1-[di(propan-2-yloxy)phosphorylmethoxy]cyclopropyl]methyl]purin-2-amine
• CAS: 693788-86-2
• 化学式: C₁₆H₂₆N₅O₄P
• 分子量: 383.387
• InChiKey: GJLYPFDLLXYKJM-UHFFFAOYSA-N

物化性质

• 沸点：
  572.1±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  26
• 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-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate 在 三甲基溴硅烷 、 三乙胺 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 66.5h， 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-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate 在 5%-palladium/activated carbon 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 diisopropyl ({1-[(2-amino-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

• J. Med. Chem. 2004, 47, 2864-2869
  作者：

  DOI：——

  日期：——
• [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。
• A Novel Class of Phosphonate Nucleosides. 9-[(1-Phosphonomethoxycyclopropyl)methyl]guanine as a Potent and Selective Anti-HBV Agent
  作者：Jong-Ryoo Choi、Dong-Gyu Cho、Kee Y. Roh、Jae-Taeg Hwang、Sinbyoung Ahn、Hyun S. Jang、Woo-Young Cho、Kyong W. Kim、Young-Gyo Cho、Jeongmin Kim、Yong-Zu Kim

  DOI：10.1021/jm0305265

  日期：2004.5.1

  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.