[1-[5'-O-(tert-butyldimethylsilyl)-2'-O-(thexyldimethylsilyl)-β-D-ribofuranosyl]-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide] | 1056297-91-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1-[5'-O-(tert-butyldimethylsilyl)-2'-O-(thexyldimethylsilyl)-β-D-ribofuranosyl]-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide]
• 英文别名: N-[[(5R,6R,8R,9R)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-9-[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxy-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-4-yl]carbamoyl]benzamide；N-[[(5R,6R,8R,9R)-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-9-[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxy-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-4-yl]carbamoyl]benzamide
• CAS: 1056297-91-6
• 化学式: C₃₅H₅₄N₄O₁₀SSi₂
• 分子量: 779.072
• InChiKey: WRKDFYGJAGDFSC-CEUBKNRQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.88
• 重原子数：
  52
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  178
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  [1-[5'-O-(tert-butyldimethylsilyl)-2'-O-(thexyldimethylsilyl)-β-D-ribofuranosyl]-3-N-methylthymine]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole-2'',2''-dioxide] 、 苯甲酰异氰酸脂 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以64%的产率得到[1-[5'-O-(tert-butyldimethylsilyl)-2'-O-(thexyldimethylsilyl)-β-D-ribofuranosyl]-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide]
  参考文献：
  名称：

  4′′-Benzoylureido-TSAO Derivatives as Potent and Selective Non-Nucleoside HCMV Inhibitors. Structure−Activity Relationship and Mechanism of Antiviral Action

  摘要：

  Analogues of the 4"-benzoyl-ureido-TSAO derivative (1) modified at different positions have been prepared and evaluated against wild-type strains of HCMV and murine cytomegalovirus (MCMV) in cell culture. In addition, the activity of the most active derivatives against several drug-resistant HCMV mutants has been determined. A stringent structure-antiviral activity relationship was observed for the 4"-benzoylureido-TSAO derivatives for which the concomitant presence of a highly lipophilic substituent at both 2'- and 5'-positions was required to fully preserve the antihuman cytomegalovirus efficacy. Time-of-addition studies and HCMV immediately early and early gene expression studies revealed a target at the time of viral DNA synthesis, although direct inhibition of HCMV-encoded DNA polymerase could not be observed in cell-free assays. Lack of cross-resistance against a broad variety of mutant HCMV strains points to an antiviral target that is different from those drugs that are currently approved for clinical use.

  DOI：

  10.1021/jm800050t