[1-(2'-O-acetyl-5'-O-benzoyl-β-D-ribofuranosyl)-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide] | 1039540-41-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1-(2'-O-acetyl-5'-O-benzoyl-β-D-ribofuranosyl)-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide]
• 英文别名: [(5R,6R,8R,9R)-9-acetyloxy-4-(benzoylcarbamoylamino)-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-6-yl]methyl benzoate；[(5R,6R,8R,9R)-9-acetyloxy-4-(benzoylcarbamoylamino)-8-(3,5-dimethyl-2,4-dioxopyrimidin-1-yl)-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-6-yl]methyl benzoate
• CAS: 1039540-41-4
• 化学式: C₃₀H₂₈N₄O₁₂S
• 分子量: 668.638
• InChiKey: LEGUKRBVZXBVJI-KKHBRMCTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  47
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  212
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [1-(2'-O-acetyl-5'-O-benzoyl-β-D-ribofuranosyl)-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide] 在 甲醇 、 氨 作用下， 反应 1.0h， 以90%的产率得到[1-(5'-O-benzoyl-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
• 作为产物：
  描述：

  [1-(2'-O-acetyl-5'-O-benzoyl-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 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以91%的产率得到[1-(2'-O-acetyl-5'-O-benzoyl-β-D-ribofuranosyl)-3-N-methylthymine]-3'-spiro-5''-[4''-(3-benzoylureido)-1'',2''-oxathiole-2'',2''-dioxide]
  参考文献：
  名称：

  Novel Non-Nucleoside Human Cytomegalovirus Inhibitors Based Upon Tsao Nucleoside Derivatives: Structure-Activity Relationships

  摘要：

  TSAO derivatives area unique group of potent and highly specific inhibitors of HIV-1 replication. We have recently reported 4"-ureido TSAO derivatives that are devoid of anti-HIV-1 activity, but inhibit human cytomegalovirus with an activity comparable to that of Ganciclovir. We herein report the synthesis and biological evaluation of novel 4"-ureido TSAO derivatives in order to evaluate the structural features required for anti-HCMV activity. Interestingly, these studies revealed that the compounds may inhibit HCMV at the DNA polymease step via a non-nucleaside mechanism.

  DOI：

  10.1080/15257770701490431

文献信息

• Novel Non-Nucleoside Human Cytomegalovirus Inhibitors Based Upon Tsao Nucleoside Derivatives: Structure-Activity Relationships
  作者：Sonia de Castro、Graziela Andrei、Robert Snoeck、Jan Balzarini、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1080/15257770701490431

  日期：2007.11.26

  TSAO derivatives area unique group of potent and highly specific inhibitors of HIV-1 replication. We have recently reported 4"-ureido TSAO derivatives that are devoid of anti-HIV-1 activity, but inhibit human cytomegalovirus with an activity comparable to that of Ganciclovir. We herein report the synthesis and biological evaluation of novel 4"-ureido TSAO derivatives in order to evaluate the structural features required for anti-HCMV activity. Interestingly, these studies revealed that the compounds may inhibit HCMV at the DNA polymease step via a non-nucleaside mechanism.
• 4′′-Benzoylureido-TSAO Derivatives as Potent and Selective Non-Nucleoside HCMV Inhibitors. Structure−Activity Relationship and Mechanism of Antiviral Action
  作者：Sonia de Castro、M. Teresa Peromingo、Lieve Naesens、Graciela Andrei、Robert Snoeck、Jan Balzarini、Sonsoles Velázquez、María-José Camarasa

  DOI：10.1021/jm800050t

  日期：2008.9.25

  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.