N⁴-benzoyl-1-[2-O-(tert-butyldimethylsilyl)-5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine | 159981-11-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N⁴-benzoyl-1-[2-O-(tert-butyldimethylsilyl)-5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine
• 英文别名: N-benzoyI-1-[S-(4,4'-dimethoxytrityl)-2-(t-butyIdimethylsilyl)-4-thio-β-D-ribofuranosyl]cytosine；N-[1-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[tert-butyl(dimethyl)silyl]oxy-4-hydroxythiolan-2-yl]-2-oxopyrimidin-4-yl]benzamide
• CAS: 159981-11-0
• 化学式: C₄₃H₄₉N₃O₇SSi
• 分子量: 780.029
• InChiKey: FPXOSNHKBGCNNC-PKGPUZNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.89
• 重原子数：
  55
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  氯(二异丙基氨基)甲氧基膦 、 N⁴-benzoyl-1-[2-O-(tert-butyldimethylsilyl)-5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine 以 二氯甲烷 为溶剂， 生成 Diisopropyl-phosphoramidous acid (2R,3S,4R,5R)-5-(4-benzoylamino-2-oxo-2H-pyrimidin-1-yl)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-thiophen-3-yl ester methyl ester
  参考文献：
  名称：

  4'-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties

  摘要：

  The syntheses and the study of nuclease resistance and hydrogen bonding of modified oligoribonucleotides, i.e. 4'-thio-beta-D-oligoribonucleotides (4'-S-RNA), are reported.

  DOI：

  10.1080/15257779508012526
• 作为产物：
  描述：

  N⁴-benzoyl-1-[5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine 在 吡啶 、 咪唑 、 silver nitrate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 N⁴-benzoyl-1-[2-O-(tert-butyldimethylsilyl)-5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine
  参考文献：
  名称：

  Improving RNA Interference in Mammalian Cells by 4‘-Thio-Modified Small Interfering RNA (siRNA):  Effect on siRNA Activity and Nuclease Stability When Used in Combination with 2‘-O-Alkyl Modifications

  摘要：

  A systematic structure-activity relationship study of 4'-thioribose containing small interfering RNAs (siRNAs) has led to the identification of highly potent and stable antisense constructs. To enable this optimization effort for both in vitro and in vivo applications, we have significantly improved the yields of 4'-thioribonucleosides by using a chirally pure (R)-sulfoxide precursor. siRNA duplexes containing strategically placed regions of 4'-thio-RNA were synthesized and evaluated for RNA interference activity and plasma stability. Stretches of 4'-thio-RNA were well tolerated in both the antisense and sense strands. However, optimization of both the number and placement of X-thioribonucleosides was necessary for maximal potency. These optimized siRNAs were generally equipotent or superior to native siRNAs and exhibited increased thermal and plasma stability. Furthermore, significant improvements in siRNA activity and plasma stability were achieved by judicious combination of 4'-thioribose with 2'-O-methyl and 2'-O-methoxyethyl modifications. These optimized 4'-thio-siRNAs may be valuable for developing stable siRNAs for therapeutic applications.

  DOI：

  10.1021/jm050822c

文献信息

• [EN] 4'-THIONUCLEOSIDES AND OLIGOMERIC COMPOUNDS<br/>[FR] 4'-THIONUCLEOSIDES ET COMPOSES D'OLIGOMERES
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2005027962A3

  公开（公告）日：2007-07-12
• 4'-Thio-β-D-oligoribonucleotides: Nuclease Resistance and Hydrogen Bonding Properties
  作者：C. Leydier、L. Bellon、J. -L. Barascut、J. -L. Imbach

  DOI：10.1080/15257779508012526

  日期：1995.5.1

  The syntheses and the study of nuclease resistance and hydrogen bonding of modified oligoribonucleotides, i.e. 4'-thio-beta-D-oligoribonucleotides (4'-S-RNA), are reported.
• Improving RNA Interference in Mammalian Cells by 4‘-Thio-Modified Small Interfering RNA (siRNA):  Effect on siRNA Activity and Nuclease Stability When Used in Combination with 2‘-<i>O</i>-Alkyl Modifications
  作者：Prasad Dande、Thazha P. Prakash、Namir Sioufi、Hans Gaus、Russell Jarres、Andreas Berdeja、Eric E. Swayze、Richard H. Griffey、Balkrishen Bhat

  DOI：10.1021/jm050822c

  日期：2006.3.1

  A systematic structure-activity relationship study of 4'-thioribose containing small interfering RNAs (siRNAs) has led to the identification of highly potent and stable antisense constructs. To enable this optimization effort for both in vitro and in vivo applications, we have significantly improved the yields of 4'-thioribonucleosides by using a chirally pure (R)-sulfoxide precursor. siRNA duplexes containing strategically placed regions of 4'-thio-RNA were synthesized and evaluated for RNA interference activity and plasma stability. Stretches of 4'-thio-RNA were well tolerated in both the antisense and sense strands. However, optimization of both the number and placement of X-thioribonucleosides was necessary for maximal potency. These optimized siRNAs were generally equipotent or superior to native siRNAs and exhibited increased thermal and plasma stability. Furthermore, significant improvements in siRNA activity and plasma stability were achieved by judicious combination of 4'-thioribose with 2'-O-methyl and 2'-O-methoxyethyl modifications. These optimized 4'-thio-siRNAs may be valuable for developing stable siRNAs for therapeutic applications.