<1-<2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl>-5-<(methyloxy)carbonyl>-1,2,3-triazole>-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) | 160261-75-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 三唑核糖核苷和核糖核苷酸
• 英文名称: <1-<2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl>-5-<(methyloxy)carbonyl>-1,2,3-triazole>-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
• 英文别名: methyl 3-[(5R,6R,8R,9R)-4-amino-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dioxo-1,7-dioxa-2lambda6-thiaspiro[4.4]non-3-en-8-yl]triazole-4-carboxylate；methyl 3-[(5R,6R,8R,9R)-4-amino-9-[tert-butyl(dimethyl)silyl]oxy-6-[[tert-butyl(dimethyl)silyl]oxymethyl]-2,2-dioxo-1,7-dioxa-2λ6-thiaspiro[4.4]non-3-en-8-yl]triazole-4-carboxylate
• CAS: 160261-75-6
• 化学式: C₂₃H₄₂N₄O₈SSi₂
• 分子量: 590.845
• InChiKey: GXYJZBPRUGMXRK-ISJRUSPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.27
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  <1-<2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl>-5-<(methyloxy)carbonyl>-1,2,3-triazole>-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) 在 氨 作用下， 以58%的产率得到<1-<2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl>-5-carbamoyl-1,2,3-triazole>-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
  参考文献：
  名称：

  1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) Analogs: Synthesis and Anti-HIV-1 Activity

  摘要：

  Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead com pound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5''(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3-spiro-5'-(4'-amino- and and 4'-(N-acetylamino)1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved superior to the unsubstituted derivative by 1-2 orders of magnitude. In particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3-triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50% effective concentration: 0.056-0.52 mu M). They show a similar resistance spectrum as previously noted for TSAO-T and related derivatives.

  DOI：

  10.1021/jm00050a015
• 作为产物：
  描述：

  在 4-二甲氨基吡啶 、 甲胺 作用下， 以 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 34.0h， 生成 <1-<2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl>-5-<(methyloxy)carbonyl>-1,2,3-triazole>-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
  参考文献：
  名称：

  1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) Analogs: Synthesis and Anti-HIV-1 Activity

  摘要：

  Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead com pound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5''(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3-spiro-5'-(4'-amino- and and 4'-(N-acetylamino)1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved superior to the unsubstituted derivative by 1-2 orders of magnitude. In particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3-triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50% effective concentration: 0.056-0.52 mu M). They show a similar resistance spectrum as previously noted for TSAO-T and related derivatives.

  DOI：

  10.1021/jm00050a015

文献信息

• TSAO Derivatives: Highly Specific Inhibitors of Human Immunodeficiency Virus Type-1 (HIV-1) Replication
  作者：Maria Camarasa、Maria Péarez-Péarez、Sonsoles Velázquez、Ana San-Féalix、Rosa Alvarez、Simon Ingate、Maria Luisa Jimeno、Anna Karlsson、Erik De Clercq、Jan Balzarini

  DOI：10.1080/15257779508012432

  日期：1995.5.1

  TSAO derivatives represent a unique class of nucleosides that are specifically targeted at HIV-1 RT. This overview is focussed on the chemical synthesis, the conformational studies, the antiviral and metabolic properties of TSAO derivatives, as well as their mechanism of antiviral action and the molecular basis of the vapid selection of resistant HIV-1 strains that emerge in cell culture in the presence of TSAO derivatives.
• Synthesis and Anti-HIV-1 Activity of 4- and 5-Substituted 1,2,3-Triazole-TSAO Derivatives
  作者：Ana San-Féalix、Rosa Alvarez、Sonsoles Veláazquez、Erik De Clercq、Jan Balzarini、María José Camarasa

  DOI：10.1080/15257779508012433

  日期：1995.5.1

  Several 4- or 5-monosubstituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead compound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5 ''-(4 ''-amino-1 '',2 ''-oxathiole-2 '',2 ''-dionide) (TSAO-T) have been prepared and evaluated for their inhibitory effect against HIV-1-induced cytopathicity.
• 1,2,3-Triazole-[2,5-Bis-O-(tert-butyldimethylsilyl)-.beta.-D-ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO) Analogs: Synthesis and Anti-HIV-1 Activity
  作者：Rosa Alvarez、Sonsoles Velazquez、Ana San-Felix、Stefano Aquaro、Erik De Clercq、Carlo-Federico Perno、Anna Karlsson、Jan Balzarini、Maria Jose Camarasa

  DOI：10.1021/jm00050a015

  日期：1994.11

  Several 4- or 5-monosubsituted and 4,5-disubstituted 1,2,3-triazole analogues of the anti-HIV-1 lead com pound [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]thymine]-3'-spiro-5''(4''-amino-1'',2''-oxathiole 2'',2''-dioxide) (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1-induced cytopathicity. These analogues have been prepared by 1,3-diplar cycloaddition of [2,5-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3-spiro-5'-(4'-amino- and and 4'-(N-acetylamino)1',2'-oxathiole 2',2'-dioxide) (TSAO) azides to various substituted acetylenes. Several 4- and 5-substituted 1,2,3-triazole-TSAO analogues proved superior to the unsubstituted derivative by 1-2 orders of magnitude. In particular the 5-substituted amido-, (methylamido)-, and (dimethylamido)-1,2,3-triazole derivatives of TSAO were endowed with potent anti-HIV-1 activity (50% effective concentration: 0.056-0.52 mu M). They show a similar resistance spectrum as previously noted for TSAO-T and related derivatives.