diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate | 441784-84-5

• 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
• 英文名称: diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate
• 英文别名: diisopropyl {[1-({[t-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate；Bis(1-methylethyl) P-[[[1-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]cyclopropyl]oxy]methyl]phosphonate；tert-butyl-[[1-[di(propan-2-yloxy)phosphorylmethoxy]cyclopropyl]methoxy]-diphenylsilane
• CAS: 441784-84-5
• 化学式: C₂₇H₄₁O₅PSi
• 分子量: 504.679
• InChiKey: IQDPTDXVDCUTKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.11
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate 在 palladium on activated charcoal 氟化铵 、 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 、 甲醇 、 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 93.5h， 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：

  1-[[[(1,1-二甲乙基)二苯基甲硅烷基]氧基]甲基]-环丙醇 以70的产率得到diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate
  参考文献：
  名称：

  [EN] NOVEL ACYCLIC NUCLEOSIDE PHOSPHONATE DERIVATIVES, SALTS THEREOF AND PROCESS FOR THE PREPARATION OF THE SAME
  [FR] NOUVEAUX DERIVES DE PHOSPHONATE NUCLEOSIDIQUE ACYCLIQUE, SELS DE CES DERNIERS ET PROCEDE DE PREPARATION DE CES DERNIERS

  摘要：

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

  公开号：

  WO2002057288A1

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

  DOI：——

  日期：——
• Drugs Fut. 2004, 29, 163
  作者：

  DOI：——

  日期：——
• 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.
• [EN] NOVEL ACYCLIC NUCLEOSIDE PHOSPHONATE DERIVATIVES, SALTS THEREOF AND PROCESS FOR THE PREPARATION OF THE SAME<br/>[FR] NOUVEAUX DERIVES DE PHOSPHONATE NUCLEOSIDIQUE ACYCLIQUE, SELS DE CES DERNIERS ET PROCEDE DE PREPARATION DE CES DERNIERS
  申请人：LG CHEM INVESTMENT LTD

  公开号：WO2002057288A1

  公开（公告）日：2002-07-25

  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，其作为抗病毒剂（特别是对乙型肝炎病毒）有用，药学上可接受的盐，立体异构体以及其制备方法。