3-(hexadecyloxy)propyl (((2R,4R)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1,3-dioxolan-2-yl)methyl) phosphonate | 883989-38-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 3-(hexadecyloxy)propyl (((2R,4R)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1,3-dioxolan-2-yl)methyl) phosphonate
• CAS: 883989-38-6
• 化学式: C₂₈H₅₁N₂O₈P
• 分子量: 574.695
• InChiKey: ZISHDYXYIXEBKR-CLJLJLNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.03
• 重原子数：
  39.0
• 可旋转键数：
  24.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  118.08
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  3-(hexadecyloxy)propyl (((2R,4R)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1,3-dioxolan-2-yl)methyl) phosphonate 、 甘氨酸甲酯盐酸盐 在 三乙胺 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 生成 {(3-Hexadecyloxy-propoxy)-[(2R,4R)-4-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-[1,3]dioxolan-2-ylmethoxy]-phosphorylamino}-acetic acid methyl ester
  参考文献：
  名称：

  Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies

  摘要：

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.008
• 作为产物：
  描述：

  十六烷基,1-3 丙二醇醚 、 亚磷酸二苯酯 、 dioxolanethymidine 在 吡啶 作用下， 反应 3.5h， 以70%的产率得到3-(hexadecyloxy)propyl (((2R,4R)-4-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-1,3-dioxolan-2-yl)methyl) phosphonate
  参考文献：
  名称：

  Phosphoramidate and phosphate prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine: Synthesis, anti-HIV activity and stability studies

  摘要：

  A series of phosphoramidate and phosphate prodrugs of DOT were synthesized via dichlorophosphate or H-phosphonate chemistry and evaluated for their anti-HIV activity against LAI M 184V mutants in PBM cells as well as for their cytotoxicity. The antiviral and cytotoxic profiles of the prodrugs were compared with that of the parent compound (DOT), and it was found that four aryl phosphoramidates 5, 18, 20, and 26 showed a significant enhancement (8- to 12-fold) in anti-HIV activity without cytotoxicity. Chemical stability of these prodrugs was evaluated in phosphate buffer at pH values of biological relevance (i.e., pH 2.0 and 7.4). Enzymatic hydrolysis was also studied in esterase or lipase in buffer solution. Chemical stability studies indicate that the phosphoramidates have good chemical stability at pH 2.0 and at pH 7.4 phosphate buffer. Phosphoramidate prodrugs were hydrolyzed in vitro by esterase or lipase and found to be better substrates for lipases than for esterases. 1,3-Diol cyclic phosphates showed potent anti-HIV activity without increasing the cytotoxicity compared with that of DOT and have good chemical and enzymatic stability. Long-chain lipid phosphates, although showed potent anti-HIV activity, exhibited increased cytotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.008