dioxolane-thymine 5'-O-cyclopropanecarboxylic ester | 1138242-29-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: dioxolane-thymine 5'-O-cyclopropanecarboxylic ester
• 英文别名: [(2R,4R)-4-(5-methyl-2,4-dioxopyrimidin-1-yl)-1,3-dioxolan-2-yl]methyl cyclopropanecarboxylate
• CAS: 1138242-29-1
• 化学式: C₁₃H₁₆N₂O₆
• 分子量: 296.28
• InChiKey: MCWNWRGXGUUDPC-NXEZZACHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  dioxolanethymidine 、 环丙甲酸 在 4-二甲氨基吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到dioxolane-thymine 5'-O-cyclopropanecarboxylic ester
  参考文献：
  名称：

  5′-O-Aliphatic and amino acid ester prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine (DOT): Synthesis, anti-HIV activity, cytotoxicity and stability studies

  摘要：

  A series of (-)-beta-D-(2R, 4R)-dioxolane-thymine-5'-O-aliphatic acid esters as well as amino acid esters were synthesized as prodrugs of (-)-beta-D-(2R, 4R)-dioxolane-thymine (DOT). The compounds were evaluated for anti-HIV activity against HIV-1(LAI) in human peripheral blood mononuclear (PBM) cells as well as for their cytotoxicity in PBM, CEM and Vero cells. Improved anti-HIV potency in vitro was observed for the compound 2-4 (5'-O-aliphatic acid esters) without increase in cytotoxicity in comparison to the parent drug. Chemical and enzymatic hydrolysis of the prodrugs was also studied, in which the prodrugs exhibited good chemical stability with the half-lives from 3 h to 54 h at pH 2.0 and 7.4 phosphate buffer. However, the prodrugs were relatively labile to porcine esterase with the half-lives from 12.3 to 48.0 min. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.10.078

文献信息

• 5′-O-Aliphatic and amino acid ester prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine (DOT): Synthesis, anti-HIV activity, cytotoxicity and stability studies
  作者：Yuzeng Liang、Ashoke Sharon、Jason P. Grier、Kimberly L. Rapp、Raymond F. Schinazi、Chung K. Chu

  DOI：10.1016/j.bmc.2008.10.078

  日期：2009.2

  A series of (-)-beta-D-(2R, 4R)-dioxolane-thymine-5'-O-aliphatic acid esters as well as amino acid esters were synthesized as prodrugs of (-)-beta-D-(2R, 4R)-dioxolane-thymine (DOT). The compounds were evaluated for anti-HIV activity against HIV-1(LAI) in human peripheral blood mononuclear (PBM) cells as well as for their cytotoxicity in PBM, CEM and Vero cells. Improved anti-HIV potency in vitro was observed for the compound 2-4 (5'-O-aliphatic acid esters) without increase in cytotoxicity in comparison to the parent drug. Chemical and enzymatic hydrolysis of the prodrugs was also studied, in which the prodrugs exhibited good chemical stability with the half-lives from 3 h to 54 h at pH 2.0 and 7.4 phosphate buffer. However, the prodrugs were relatively labile to porcine esterase with the half-lives from 12.3 to 48.0 min. (C) 2008 Elsevier Ltd. All rights reserved.