{3-[(5R,6R,8R,9R)-4-Amino-9-(tert-butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-acetic acid | 263843-31-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: {3-[(5R,6R,8R,9R)-4-Amino-9-(tert-butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-acetic acid
• 英文别名: 2-[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]-5-methyl-2,6-dioxopyrimidin-1-yl]acetic acid；2-[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]-5-methyl-2,6-dioxopyrimidin-1-yl]acetic acid
• CAS: 263843-31-8
• 化学式: C₂₆H₄₅N₃O₁₀SSi₂
• 分子量: 647.894
• InChiKey: YNHWBVLIRJDSMX-JDFPCGKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.61
• 重原子数：
  42
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  183
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  二(2-氯乙基)氯化铵 、 {3-[(5R,6R,8R,9R)-4-Amino-9-(tert-butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-acetic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以68%的产率得到[1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[[N,N-bis(2-chloroethyl)carbamoyl]methyl]thymine]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)
  参考文献：
  名称：

  Novel N-3 Substituted TSAO-T Derivatives: Synthesis and Anti-HIV-Evaluation

  摘要：

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position alkylating groups or photoaffinity labels were prepared and evaluated for their anti-HIV activity. All of these compounds demonstrated pronounced anti-HIV-1 activity and inhibited HIV-1 RT; however, we were unable to detect stable covalent linkages between inhibitor and enzyme. In addition, compounds with an alcohol functional group connected to the N-3 position through a cis or trans double bond have been prepared. These compounds have been useful to study how the conformational restriction of the linker affects in the interaction between the N-3 substituent and the HIV-1 RT enzyme.

  DOI：

  10.1080/15257770801943990
• 作为产物：
  描述：

  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-2-硫杂螺[4.4]壬-3-烯-7-基]-5-甲基嘧啶-2,4-二酮 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 {3-[(5R,6R,8R,9R)-4-Amino-9-(tert-butyl-dimethyl-silanyloxy)-6-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dioxo-1,7-dioxa-2λ⁶-thia-spiro[4.4]non-3-en-8-yl]-5-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl}-acetic acid
  参考文献：
  名称：

  Improving the Antiviral Efficacy and Selectivity of HIV-1 Reverse Transcriptase Inhibitor TSAO-T by the Introduction of Functional Groups at the N-3 Position

  摘要：

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position a variety of polar, lipophilic, or aromatic groups linked to that position through flexible polymethylene linkers of different length, were prepared and evaluated for their anti-HIV activity. Several compounds (within the series of polar bearing groups) exhibited a 2-6-fold improved antiviral potency with regard to the lead compound, TSAO-T. Moreover, some of the most active N-3 TSAO derivatives retain antiviral activity against the TSAO-T-resistant HIV-1 strain (Glu138 -> Lys). Interestingly, the N-methylcarboxamide derivative 17 was 5- to 6-fold more active (IC50: 0.56 mu M) against recombinant HIV-1 reverse transcriptase than the lead compound, thus becoming the most active TSAO derivative synthesized so far. On the other hand, the N-3 methylcarboxamide TSAO derivative 12 turned out to have the highest selectivity index yet reported for this class of compounds (around >= 12 000).

  DOI：

  10.1021/jm050437n

文献信息

• Improving the Antiviral Efficacy and Selectivity of HIV-1 Reverse Transcriptase Inhibitor TSAO-T by the Introduction of Functional Groups at the N-3 Position
  作者：María-Cruz Bonache、Cristina Chamorro、Sonsoles Velázquez、Erik De Clercq、Jan Balzarini、Fátima Rodríguez Barrios、Federico Gago、María-José Camarasa、Ana San-Félix

  DOI：10.1021/jm050437n

  日期：2005.10.1

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position a variety of polar, lipophilic, or aromatic groups linked to that position through flexible polymethylene linkers of different length, were prepared and evaluated for their anti-HIV activity. Several compounds (within the series of polar bearing groups) exhibited a 2-6-fold improved antiviral potency with regard to the lead compound, TSAO-T. Moreover, some of the most active N-3 TSAO derivatives retain antiviral activity against the TSAO-T-resistant HIV-1 strain (Glu138 -> Lys). Interestingly, the N-methylcarboxamide derivative 17 was 5- to 6-fold more active (IC50: 0.56 mu M) against recombinant HIV-1 reverse transcriptase than the lead compound, thus becoming the most active TSAO derivative synthesized so far. On the other hand, the N-3 methylcarboxamide TSAO derivative 12 turned out to have the highest selectivity index yet reported for this class of compounds (around >= 12 000).
• Novel N-3 Substituted TSAO-T Derivatives: Synthesis and Anti-HIV-Evaluation
  作者：María-Cruz Bonache、Ernesto Quesada、Chih-Wei Sheen、Jan Balzarini、Nicolas Sluis-Cremer、María Jesús Pérez-Pérez、María-José Camarasa、Ana San-Félix

  DOI：10.1080/15257770801943990

  日期：2008.4.4

  Novel derivatives of the anti-HIV-1 agent, TSAO-T, bearing at the N-3 position alkylating groups or photoaffinity labels were prepared and evaluated for their anti-HIV activity. All of these compounds demonstrated pronounced anti-HIV-1 activity and inhibited HIV-1 RT; however, we were unable to detect stable covalent linkages between inhibitor and enzyme. In addition, compounds with an alcohol functional group connected to the N-3 position through a cis or trans double bond have been prepared. These compounds have been useful to study how the conformational restriction of the linker affects in the interaction between the N-3 substituent and the HIV-1 RT enzyme.