(E)-bis-(POM)-4-bromobut-en-1-yl phosphonate | 1365350-40-8

• 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: (E)-bis-(POM)-4-bromobut-en-1-yl phosphonate
• 英文别名: [[(E)-4-bromobut-2-enyl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
• CAS: 1365350-40-8
• 化学式: C₁₆H₂₈BrO₇P
• 分子量: 443.272
• InChiKey: YAPDYKRLAFSZEM-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (E)-bis-(POM)-4-bromobut-en-1-yl phosphonate 在 sodium azide 、 铜 、 copper(II) sulfate 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 32.0h， 生成 C₂₄H₃₃FN₃O₇P
  参考文献：
  名称：

  新型无环核苷双(POM)前药的合成及广谱抗病毒评价

  摘要：

  一系列迄今未知的 ANP 类似物，带有 ( E )-but-2-enyl 脂肪族侧链和修饰的杂环碱基，例如胞嘧啶和 5-氟胞嘧啶、2-吡嗪甲酰胺、1,2,4-三唑-3-甲酰胺或4-取代-1,2,3-三唑通过烯烃无环交叉复分解作为关键合成步骤直接制备。 评估了所有新化合物对大量 DNA 和 RNA 病毒的抗病毒活性，包括单纯疱疹病毒 1 型和 2 型、水痘带状疱疹病毒、猫疱疹病毒、人类巨细胞病毒、丙型肝炎病毒 (HCV)、HIV-1 和 HIV -2。在这些分子中，只有化合物31在 HEL 细胞培养物中显示出对人巨细胞病毒的活性，EC 50为～10 μM。化合物8a、13、14和24在100 μM时表现出显着的抗 HCV 活性而没有显着的细胞毒性。

  DOI：

  10.1016/j.ejmech.2013.06.053
• 作为产物：
  描述：

  烯丙基磷酸二甲酯 在 [1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(benzylidene)(triphenylphosphine) ruthenium(II) 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 60.0h， 生成 (E)-bis-(POM)-4-bromobut-en-1-yl phosphonate
  参考文献：
  名称：

  Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4′-phosphono-but-2′-en-1′-yl]purine nucleosides

  摘要：

  Seventeen hitherto unknown bis(POM) prodrugs of novel (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides were prepared in a straight approach and at good yields. Those compounds were synthesized by the reaction of purine nucleobases directly with the phosphonate synthon 3 bearing POM biolabile groups under Mitsunobu conditions. All obtained compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex viruses 1 and 2, varicella zoster virus, Feline herpes virus, human cytomegalovirus, HIV-1 and HIV-2. Among these molecules, some of them exhibit anti-VZV and anti-HIV activity at submicromolar concentrations. This class of compound will be of further interest for lead optimization as anti-infectious agents. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.08.042

文献信息

• [EN] NOVEL ANTIVIRAL ACYCLIC NUCLEOSIDE PHOSPHONATES<br/>[FR] NOUVEAUX PHOSPHONATES DE NUCLÉOSIDES ACYCLIQUES ANTIVIRAUX
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2012034719A1

  公开（公告）日：2012-03-22

  Compounds of formula (I) wherein A represents a nucleobase or a derivative thereof, n is equal to 0 or 1 and R', R" are carbonic chain, and R10 is hydrogen or a carbonic chain for their use as antiviral agents.

  式(I)中A代表核碱基或其衍生物，n等于0或1，R'、R"为碳链，R10为氢或碳链，用作抗病毒剂。
• PHOSPHONATES SYNTHONS FOR THE SYNTHESIS OF PHOSPHONATES DERIVATIVES SHOWING BETTER BIOAVAILABILITY
  申请人：Agrofoglio Luigi A.

  公开号：US20120142897A1

  公开（公告）日：2012-06-07

  Synthons for the synthesis of phosphonates prodrugs POM and POC, especially for direct Cross Metathesis.
• US8785629B2
  申请人：——

  公开号：US8785629B2

  公开（公告）日：2014-07-22
• Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4′-phosphono-but-2′-en-1′-yl]purine nucleosides
  作者：Ugo Pradère、Vincent Roy、Aurélien Montagu、Ozkan Sari、Manabu Hamada、Jan Balzarini、Robert Snoeck、Graciela Andrei、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2012.08.042

  日期：2012.11

  Seventeen hitherto unknown bis(POM) prodrugs of novel (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides were prepared in a straight approach and at good yields. Those compounds were synthesized by the reaction of purine nucleobases directly with the phosphonate synthon 3 bearing POM biolabile groups under Mitsunobu conditions. All obtained compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex viruses 1 and 2, varicella zoster virus, Feline herpes virus, human cytomegalovirus, HIV-1 and HIV-2. Among these molecules, some of them exhibit anti-VZV and anti-HIV activity at submicromolar concentrations. This class of compound will be of further interest for lead optimization as anti-infectious agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides
  作者：Manabu Hamada、Vincent Roy、Tamara R. McBrayer、Tony Whitaker、Cesar Urbina-Blanco、Steven P. Nolan、Jan Balzarini、Robert Snoeck、Graciela Andrei、Raymond F. Schinazi、Luigi A. Agrofoglio

  DOI：10.1016/j.ejmech.2013.06.053

  日期：2013.9

  synthetic step. All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50

  一系列迄今未知的 ANP 类似物，带有 ( E )-but-2-enyl 脂肪族侧链和修饰的杂环碱基，例如胞嘧啶和 5-氟胞嘧啶、2-吡嗪甲酰胺、1,2,4-三唑-3-甲酰胺或4-取代-1,2,3-三唑通过烯烃无环交叉复分解作为关键合成步骤直接制备。 评估了所有新化合物对大量 DNA 和 RNA 病毒的抗病毒活性，包括单纯疱疹病毒 1 型和 2 型、水痘带状疱疹病毒、猫疱疹病毒、人类巨细胞病毒、丙型肝炎病毒 (HCV)、HIV-1 和 HIV -2。在这些分子中，只有化合物31在 HEL 细胞培养物中显示出对人巨细胞病毒的活性，EC 50为～10 μM。化合物8a、13、14和24在100 μM时表现出显着的抗 HCV 活性而没有显着的细胞毒性。