1-((2S,5R)-2-Hydroxymethyl-[1,3]oxathiolan-5-yl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid (2-amino-ethyl)-amide

• 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: 1-((2S,5R)-2-Hydroxymethyl-[1,3]oxathiolan-5-yl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid (2-amino-ethyl)-amide
• 英文别名: N-(2-aminoethyl)-1-[(2S,5R)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2,4-dioxo-pyrimidine-5-carboxamide；N-(2-aminoethyl)-1-[(2S,5R)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2,4-dioxopyrimidine-5-carboxamide
• 化学式: C₁₁H₁₆N₄O₅S
• 分子量: 316.338
• InChiKey: AGMDJBKWTOWILY-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (2-{[1-((S)-2-Hydroxymethyl-[1,3]oxathiolan-5-yl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonyl]-amino}-ethyl)-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以98%的产率得到1-((2S,5R)-2-Hydroxymethyl-[1,3]oxathiolan-5-yl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid (2-amino-ethyl)-amide
  参考文献：
  名称：

  Synthesis and Anti-HIV Evaluation of New 5-Substituted-2′,3′-Dideoxy-3′-thiauridine Nucleosides

  摘要：

  On the basis of molecular modeling calculations using GenMol software, new 5-substituted-2',3'-dideoxy-3'-thiauridine were designed as possible anti-HIV reverse transcriptase inhibitors. The synthesis of the key intermediate 5-carboxy-2',3'-dideoxy-3'-thiauridine was achieved through the condensation of the fully silylated 5-carboxyuracil on 2-benzoyl methyl-5-acetoxy-1,3-oxathiolane using trimethylsilyl triflate (TMSOTf). This latter compound was condensed with 2-(N-tert-Butoxycarbonyl)-1-aminoethane in the presence of N,N-diisopropylethylamine (DIEA). The subsequent carboxamide deprotection led to the final compounds. These new analogues were evaluated for their anti-HIV-1 activities on infected MT(4) cells but no significant protection was observed. Electronic and structural parameters considered in this model were not sufficient to predict any active anti-HIV molecular structures.

  DOI：

  10.1080/07328319608002439

文献信息

• Synthesis and Anti-HIV Evaluation of New 5-Substituted-2′,3′-Dideoxy-3′-thiauridine Nucleosides
  作者：Nicolas Mourier、Carole Trabaud、Valerie Niddam、Jean-Christophe Graciet、Michel Camplo、Jean-Claude Chermann、Jean-Louis Kraus

  DOI：10.1080/07328319608002439

  日期：1996.7

  On the basis of molecular modeling calculations using GenMol software, new 5-substituted-2',3'-dideoxy-3'-thiauridine were designed as possible anti-HIV reverse transcriptase inhibitors. The synthesis of the key intermediate 5-carboxy-2',3'-dideoxy-3'-thiauridine was achieved through the condensation of the fully silylated 5-carboxyuracil on 2-benzoyl methyl-5-acetoxy-1,3-oxathiolane using trimethylsilyl triflate (TMSOTf). This latter compound was condensed with 2-(N-tert-Butoxycarbonyl)-1-aminoethane in the presence of N,N-diisopropylethylamine (DIEA). The subsequent carboxamide deprotection led to the final compounds. These new analogues were evaluated for their anti-HIV-1 activities on infected MT(4) cells but no significant protection was observed. Electronic and structural parameters considered in this model were not sufficient to predict any active anti-HIV molecular structures.