3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-3-oxopropanoic acid

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-3-oxopropanoic acid
• 化学式: C₁₃H₁₅N₅O₇
• 分子量: 353.291
• InChiKey: ATNGFFAUFQWIAA-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  137
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-3-oxopropanoic acid 、 1-S-dodecyl-2-O-(8-hydroxyoctyl)-rac-thioglycero-3-phosphocholine 在 吡啶 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 反应 18.0h， 以19.9%的产率得到[2-[8-[3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-3-oxopropanoyl]oxyoctoxy]-3-dodecylsulfanylpropyl] 2-(trimethylazaniumyl)ethyl phosphate
  参考文献：
  名称：

  Synthesis and Evaluation of a Novel Synthetic Phosphocholine Lipid‐AZT Conjugate That Double‐Targets Wild‐Type and Drug Resistant Variants of HIV

  摘要：

  INK-20, a synthetic phosphocholine lipid-AZT conjugate, was evaluated for antiviral activity against wild-type HIV-1, a matched pair of pre-AZT and post-AZT and multidrug resistant clinical isolates. In addition, it was tested for activity against viruses resistant to nucleoside (AZT, 3TC) and nonnucleoside (nevirapine) reverse transcriptase and protease (saquinavir) inhibitors using the syncytial plaque reduction assay for infectious virus multiplication. The EC50 values were 0.004, and 0.005 muM against wild-type HIV-1 for INK-20 and AZT, respectively. INK-20 showed little or no cytotoxicity when assayed in CEM-SS cells and four other cell types including PBMC. This resulted in a selective index of > 25,000 and > 20,000 for INK-20 and AZT, respectively. When tested against a matched pair of pre-AZT and post-AZT clinical isolates, the EC50 values were 0.01 and 0.03 muM for INK-20 and 0.0005 and 0.33 muM for AZT, respectively. INK-20 had moderate to good activity against two other AZT resistant variants and very good activity against a multi-drug resistant clinical isolate compared to marked resistance of these viruses to AZT alone. INK-20 retained significant activity against viruses resistant to 3TC, nevirapine, and saquinavir. The synthetic phosphocholine lipid-AZT conjugate INK-20 represents a novel class of anti-HIV compounds, which may provide new strategies for the treatment of HIV drug-resistant variants.

  DOI：

  10.1081/ncn-120028335
• 作为产物：
  描述：

  齐多夫定 、 丙二酰氯 以 乙腈 为溶剂， 反应 6.5h， 以68%的产率得到3-[[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]-3-oxopropanoic acid
  参考文献：
  名称：

  Synthesis and Evaluation of a Novel Synthetic Phosphocholine Lipid‐AZT Conjugate That Double‐Targets Wild‐Type and Drug Resistant Variants of HIV

  摘要：

  INK-20, a synthetic phosphocholine lipid-AZT conjugate, was evaluated for antiviral activity against wild-type HIV-1, a matched pair of pre-AZT and post-AZT and multidrug resistant clinical isolates. In addition, it was tested for activity against viruses resistant to nucleoside (AZT, 3TC) and nonnucleoside (nevirapine) reverse transcriptase and protease (saquinavir) inhibitors using the syncytial plaque reduction assay for infectious virus multiplication. The EC50 values were 0.004, and 0.005 muM against wild-type HIV-1 for INK-20 and AZT, respectively. INK-20 showed little or no cytotoxicity when assayed in CEM-SS cells and four other cell types including PBMC. This resulted in a selective index of > 25,000 and > 20,000 for INK-20 and AZT, respectively. When tested against a matched pair of pre-AZT and post-AZT clinical isolates, the EC50 values were 0.01 and 0.03 muM for INK-20 and 0.0005 and 0.33 muM for AZT, respectively. INK-20 had moderate to good activity against two other AZT resistant variants and very good activity against a multi-drug resistant clinical isolate compared to marked resistance of these viruses to AZT alone. INK-20 retained significant activity against viruses resistant to 3TC, nevirapine, and saquinavir. The synthetic phosphocholine lipid-AZT conjugate INK-20 represents a novel class of anti-HIV compounds, which may provide new strategies for the treatment of HIV drug-resistant variants.

  DOI：

  10.1081/ncn-120028335

文献信息

• Synthesis and Evaluation of a Novel Synthetic Phosphocholine Lipid‐AZT Conjugate That Double‐Targets Wild‐Type and Drug Resistant Variants of HIV
  作者：Louis S. Kucera、Susan L. Morris‐Natschke、Khalid S. Ishaq、Jan Hes、Nathan Iyer、Phillip A. Furman、Ronald A. Fleming

  DOI：10.1081/ncn-120028335

  日期：2004.1.1

  INK-20, a synthetic phosphocholine lipid-AZT conjugate, was evaluated for antiviral activity against wild-type HIV-1, a matched pair of pre-AZT and post-AZT and multidrug resistant clinical isolates. In addition, it was tested for activity against viruses resistant to nucleoside (AZT, 3TC) and nonnucleoside (nevirapine) reverse transcriptase and protease (saquinavir) inhibitors using the syncytial plaque reduction assay for infectious virus multiplication. The EC50 values were 0.004, and 0.005 muM against wild-type HIV-1 for INK-20 and AZT, respectively. INK-20 showed little or no cytotoxicity when assayed in CEM-SS cells and four other cell types including PBMC. This resulted in a selective index of > 25,000 and > 20,000 for INK-20 and AZT, respectively. When tested against a matched pair of pre-AZT and post-AZT clinical isolates, the EC50 values were 0.01 and 0.03 muM for INK-20 and 0.0005 and 0.33 muM for AZT, respectively. INK-20 had moderate to good activity against two other AZT resistant variants and very good activity against a multi-drug resistant clinical isolate compared to marked resistance of these viruses to AZT alone. INK-20 retained significant activity against viruses resistant to 3TC, nevirapine, and saquinavir. The synthetic phosphocholine lipid-AZT conjugate INK-20 represents a novel class of anti-HIV compounds, which may provide new strategies for the treatment of HIV drug-resistant variants.