5-methyl-1-[(2R,5S)-5-[[6-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-6-yl]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione | 1160003-72-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷酸
• 英文名称: 5-methyl-1-[(2R,5S)-5-[[6-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-6-yl]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione
• 英文别名: 5-methyl-1-[(2R,5S)-5-[[6-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-6-yl]-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione
• CAS: 1160003-72-4
• 化学式: C₃₄H₃₂N₄O₁₄P₂
• 分子量: 782.594
• InChiKey: ARIHYXBNVPIFAF-MSITUHCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  54
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  207
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5-methyl-1-[(2R,5S)-5-[[6-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-6-yl]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione 生成 3'-deoxy-2',3'-didehydro-5'-O-dihydroxyphosphoryl thymidine
  参考文献：
  名称：

  Doubly Loaded cycloSaligenyl-Pronucleotides – 5,5′-Bis-(cycloSaligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates)

  摘要：

  Recently, we reported on 3,3'-bis-(cycloSaligenyl-2',3'-dideoxy-2',3'-didehydrothymidine monophosphates) (3,3'-bis-(cycloSal-d4TMPs) 4) as the first pronucleotides with a mask-to-drug ratio of 1:2 that is still a novelty in the field of pronucleotides. Here, we report on a new set of compounds of these unique type of cycloSaligenyl prodrugs 5 that bear a biaryl axis at the 5-position of the cycloSal residue. All compounds 5 showed pronounced in vitro activity against HIV-1 and HIV-2 in wild-type CEM cell cultures and better retained their antiviral activities in thymidine kinase-deficient CEM cells than the compound 4 series. Moreover, compound 5b is the first bis-(cycloSal-d4TMP) that even showed complete retention of antiviral activity in TK-deficient CEM cells. The complex hydrolysis behavior of 5 was investigated, and the proposed hydrolysis mechanism was proven by means of P-31 NMR spectroscopy and HPLC analysis.

  DOI：

  10.1021/jm900164g
• 作为产物：
  描述：

  在 叔丁基过氧化氢 作用下， 以 正壬烷 、 乙腈 为溶剂， 反应 1.0h， 以51 mg的产率得到5-methyl-1-[(2R,5S)-5-[[6-[2-[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-6-yl]-2-oxo-4H-1,3,2lambda5-benzodioxaphosphinin-2-yl]oxymethyl]-2,5-dihydrofuran-2-yl]pyrimidine-2,4-dione
  参考文献：
  名称：

  Doubly Loaded cycloSaligenyl-Pronucleotides – 5,5′-Bis-(cycloSaligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates)

  摘要：

  Recently, we reported on 3,3'-bis-(cycloSaligenyl-2',3'-dideoxy-2',3'-didehydrothymidine monophosphates) (3,3'-bis-(cycloSal-d4TMPs) 4) as the first pronucleotides with a mask-to-drug ratio of 1:2 that is still a novelty in the field of pronucleotides. Here, we report on a new set of compounds of these unique type of cycloSaligenyl prodrugs 5 that bear a biaryl axis at the 5-position of the cycloSal residue. All compounds 5 showed pronounced in vitro activity against HIV-1 and HIV-2 in wild-type CEM cell cultures and better retained their antiviral activities in thymidine kinase-deficient CEM cells than the compound 4 series. Moreover, compound 5b is the first bis-(cycloSal-d4TMP) that even showed complete retention of antiviral activity in TK-deficient CEM cells. The complex hydrolysis behavior of 5 was investigated, and the proposed hydrolysis mechanism was proven by means of P-31 NMR spectroscopy and HPLC analysis.

  DOI：

  10.1021/jm900164g

文献信息

• Doubly Loaded <i>cyclo</i>Saligenyl-Pronucleotides – 5,5′-Bis-(<i>cyclo</i>Saligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates)
  作者：Nicolas Gisch、Jan Balzarini、Chris Meier

  DOI：10.1021/jm900164g

  日期：2009.6.11

  Recently, we reported on 3,3'-bis-(cycloSaligenyl-2',3'-dideoxy-2',3'-didehydrothymidine monophosphates) (3,3'-bis-(cycloSal-d4TMPs) 4) as the first pronucleotides with a mask-to-drug ratio of 1:2 that is still a novelty in the field of pronucleotides. Here, we report on a new set of compounds of these unique type of cycloSaligenyl prodrugs 5 that bear a biaryl axis at the 5-position of the cycloSal residue. All compounds 5 showed pronounced in vitro activity against HIV-1 and HIV-2 in wild-type CEM cell cultures and better retained their antiviral activities in thymidine kinase-deficient CEM cells than the compound 4 series. Moreover, compound 5b is the first bis-(cycloSal-d4TMP) that even showed complete retention of antiviral activity in TK-deficient CEM cells. The complex hydrolysis behavior of 5 was investigated, and the proposed hydrolysis mechanism was proven by means of P-31 NMR spectroscopy and HPLC analysis.