[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-[4''-(3-methacryloylureido)-1'',2''-oxathiole-2'',2''-dioxide]

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-[4''-(3-methacryloylureido)-1'',2''-oxathiole-2'',2''-dioxide]
• 英文别名: N-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-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]-2-methylprop-2-enamide；N-[[(5R,6R,8R,9R)-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-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]-2-methylprop-2-enamide
• 化学式: C₃₀H₅₀N₄O₁₀SSi₂
• 分子量: 714.985
• InChiKey: WSCQSQZUQMXYOH-IOMBEJSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.51
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  甲基丙烯酰异氰酸酯 、 1-[(5R,6R,7R,9R)-4-氨基-6-(叔丁基-二甲基硅烷基)氧基-9-[(叔丁基-二甲基硅烷基)氧基甲基]-2,2-二氧代-1,8-二氧杂-2lambda6-硫杂螺[4.4]壬-3-烯-7-基]-3,5-二甲基嘧啶-2,4-二酮 以 乙腈 为溶剂， 反应 72.0h， 以75%的产率得到[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-(methyl)thymine]-3'-spiro-5''-[4''-(3-methacryloylureido)-1'',2''-oxathiole-2'',2''-dioxide]
  参考文献：
  名称：

  Novel [2‘,5‘-Bis-O-(tert-butyldimethylsilyl)-β-d-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity

  摘要：

  New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) derivatives substituted at the 4"-amino group of the spiro moiety with different carbonyl functionalities have been designed and synthesized. Various synthetic procedures, on the scarcely studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been explored. The compounds were evaluated for their inhibitory effect on both wild-type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amide groups (12) at the 4"-position conferred the highest anti-HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presence at this position of (un)substituted ureido or acyl groups markedly diminished or annihilated the anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never been observed previously for TSAO derivatives. In particular, compound 26 represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.

  DOI：

  10.1021/jm040868q

文献信息

• “SECOND GENERATION” OF TSAO COMPOUNDS DIRECTED AGAINST HIV-1 TSAO-RESISTANT STRAINS
  作者：E. Lobatón、S. Velázquez、M. J. Pérez-Pérez、M. L. Jimeno、A. San-Félix、E. De Clercq、J. Balzarini、M. J. Camarasa

  DOI：10.1081/ncn-100002356

  日期：2001.3.31

  A "second generation" of TSAO molecules directed against TSAO-resistant strains have been prepared. The presence of two neighboring carbonyl groups at the 4 " position of the 3'-spiro moiety seems to be important for the anti-HIV-1 activity against both wild type and TSAO-resistant strains. NMR conformational studies in solution and theoretical calculations of the novel compounds have also been carried out.
• Novel [2‘,5‘-Bis-<i>O-</i>(<i>tert-</i>butyldimethylsilyl)-β-<scp>d</scp>-ribofuranosyl]- 3‘-spiro-5‘ ‘-(4‘ ‘-amino-1‘ ‘,2‘ ‘-oxathiole-2‘ ‘,2‘ ‘-dioxide) Derivatives with Anti-HIV-1 and Anti-Human-Cytomegalovirus Activity
  作者：Sonia de Castro、Esther Lobatón、María-Jesús Pérez-Pérez、Ana San-Félix、Alessandra Cordeiro、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1021/jm040868q

  日期：2005.2.1

  New [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5"-(4"-amino-1",2"-oxathiole-2",2"-dioxide) (TSAO) derivatives substituted at the 4"-amino group of the spiro moiety with different carbonyl functionalities have been designed and synthesized. Various synthetic procedures, on the scarcely studied reactivity of the 3'-spiroaminooxathioledioxide moiety, have been explored. The compounds were evaluated for their inhibitory effect on both wild-type and TSAO-resistant HIV-1 strains, in cell culture. The presence of a methyl ester (10) or amide groups (12) at the 4"-position conferred the highest anti-HIV-1 activity, while the free oxalyl acid derivative (11) was 10- to 20-fold less active against the virus. In contrast, the presence at this position of (un)substituted ureido or acyl groups markedly diminished or annihilated the anti-HIV-1 activity. Surprisingly, some of the target compounds also showed inhibition of human cytomegalovirus (HCMV) replication at subtoxic concentrations. This has never been observed previously for TSAO derivatives. In particular, compound 26 represents the first TSAO derivative with dual anti-HIV-1 and -HCMV activity.