1-O-octadecyl-sn-glycero-3-phospho-N2-acetylacyclovir | 194918-93-9

• 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: 1-O-octadecyl-sn-glycero-3-phospho-N2-acetylacyclovir
• 英文别名: 1-O-octadecyl-sn-glycero-3-phospho-N²-acetylacyclovir
• CAS: 194918-93-9
• 化学式: C₃₄H₅₉N₆O₉P
• 分子量: 726.851
• InChiKey: ATCDREZZQQZWEC-BTPPFOILSA-N

物化性质

• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 重原子数：
  50.0
• 可旋转键数：
  32.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  199.91
• 氢给体数：
  3.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  1-O-octadecyl-sn-glycero-3-phospho-N2-acetylacyclovir 在 ammonium hydroxide 作用下， 以 吡啶 为溶剂， 反应 5.0h， 以92%的产率得到1-O-octadecyl-sn-glycero-3-phospho-acyclovir
  参考文献：
  名称：

  Enhanced oral absorption and antiviral activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir and related compounds in hepatitis b virus infection, in vitro

  摘要：

  Acyclovir (ACV) triphosphate and azidothymidine (AZT) triphosphate inhibit the DNA polymerase of human hepatitis B virus (HBV) by 50% at submicromolar concentrations, but no effects of ACV or AZT treatment have been noted on the clinical manifestations of hepatitis B. We synthesized 1-O-actadecyl-sn-glycero- 3-phospho-acyclovir (ODG-P-ACV), 1-O-hexadecylpropanediol-3-phospho-acyclovir (HDP P-ACV), and 1-O-octadecyl-sn-glycero-3-phospho-azidothymidine (ODG-P-AZT), and evaluated their antiviral activity in human hepatoma cells that constitutively produce HBV (2.2.15 cells). ACV and AZT up to 100 mu M caused only slight inhibition of HBV replication in 2.2.15 cells. However, HDP-P-ACV and ODG-P-ACV inhibited viral replication by 50% at 0.5 and 6.8 mu M, respectively. ODG-P-AZT also showed increased antiviral activity, with a 50% reduction in HBV replication at 2.1 mu M. Based on the EC50, HDP-P-ACV, ODG-P-ACV, and ODG-P-AZT were > 200, > 14.7, and > 48 times more active than their free nucleosides in reducing HBV replication in 2.2.15 cells. To evaluate the biochemical basis for the increased antiviral activity, we studied the uptake and metabolism of 1-O-octadecyl-sn-glycero-3-phospho-[H-3]acyclovir (ODG-P-[H-3]ACV) in HepG2 cells. Cellular uptake of ODG-P-[H-3]ACV was found to be substantially greater than that of [H-3]ACV, and cellular Levels of ACV-mono-, -di-, and -triphosphate were much higher with ODG-P-ACV. ODG-P-[H-3]ACV was well absorbed orally. Based on urinary recovery of tritium after oral or parenteral administration of the radiolabeled compounds, oral absorption of ODG-P-ACV in mice was 100% versus 37% for ACV. ODG-P-ACV plasma area under the curve was more than 7-fold greater than that of ACV. Lipid prodrugs of this type may be useful orally in treating viral diseases. (C) 1997 Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(97)82446-x
• 作为产物：
  描述：

  N2-乙酰基-9-[(2-羟基乙氧基)甲基]胍 在 N-甲基咪唑 、 苯甲基-2-磺酰三硝基三氮唑 、 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 为溶剂， 生成 1-O-octadecyl-sn-glycero-3-phospho-N2-acetylacyclovir
  参考文献：
  名称：

  Enhanced oral absorption and antiviral activity of 1-O-octadecyl-sn-glycero-3-phospho-acyclovir and related compounds in hepatitis b virus infection, in vitro

  摘要：

  Acyclovir (ACV) triphosphate and azidothymidine (AZT) triphosphate inhibit the DNA polymerase of human hepatitis B virus (HBV) by 50% at submicromolar concentrations, but no effects of ACV or AZT treatment have been noted on the clinical manifestations of hepatitis B. We synthesized 1-O-actadecyl-sn-glycero- 3-phospho-acyclovir (ODG-P-ACV), 1-O-hexadecylpropanediol-3-phospho-acyclovir (HDP P-ACV), and 1-O-octadecyl-sn-glycero-3-phospho-azidothymidine (ODG-P-AZT), and evaluated their antiviral activity in human hepatoma cells that constitutively produce HBV (2.2.15 cells). ACV and AZT up to 100 mu M caused only slight inhibition of HBV replication in 2.2.15 cells. However, HDP-P-ACV and ODG-P-ACV inhibited viral replication by 50% at 0.5 and 6.8 mu M, respectively. ODG-P-AZT also showed increased antiviral activity, with a 50% reduction in HBV replication at 2.1 mu M. Based on the EC50, HDP-P-ACV, ODG-P-ACV, and ODG-P-AZT were > 200, > 14.7, and > 48 times more active than their free nucleosides in reducing HBV replication in 2.2.15 cells. To evaluate the biochemical basis for the increased antiviral activity, we studied the uptake and metabolism of 1-O-octadecyl-sn-glycero-3-phospho-[H-3]acyclovir (ODG-P-[H-3]ACV) in HepG2 cells. Cellular uptake of ODG-P-[H-3]ACV was found to be substantially greater than that of [H-3]ACV, and cellular Levels of ACV-mono-, -di-, and -triphosphate were much higher with ODG-P-ACV. ODG-P-[H-3]ACV was well absorbed orally. Based on urinary recovery of tritium after oral or parenteral administration of the radiolabeled compounds, oral absorption of ODG-P-ACV in mice was 100% versus 37% for ACV. ODG-P-ACV plasma area under the curve was more than 7-fold greater than that of ACV. Lipid prodrugs of this type may be useful orally in treating viral diseases. (C) 1997 Elsevier Science Inc.

  DOI：

  10.1016/s0006-2952(97)82446-x