N⁴-benzoyl-1-[5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine | 159981-09-6

• 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-[5-O-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyl]cytosine
• 英文别名: N-benzoyl-1-[5-(4,4'-dimethoxytrityl)-4-thio-β-D-ribofuranosyI]cytosine；N-[1-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3,4-dihydroxythiolan-2-yl]-2-oxopyrimidin-4-yl]benzamide
• CAS: 159981-09-6
• 化学式: C₃₇H₃₅N₃O₇S
• 分子量: 665.767
• InChiKey: MSXQFJWJHLFSOZ-NHASGABXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  48
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  N-{1-[(2R,3R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3,4-bis-(tert-butyl-dimethyl-silanyloxy)-tetrahydro-thiophen-2-yl]-2-oxo-1,2-dihydro-pyrimidin-4-yl}-benzamide 在 triethylamine trihydrofluoride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以13 g的产率得到N⁴-benzoyl-1-[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

• 4'-thionucleosides and oligomeric compounds
  申请人：Bhat Balkrishen

  公开号：US20050130923A1

  公开（公告）日：2005-06-16

  The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.

  本发明提供了经过修饰的寡核苷酸化合物和寡核苷酸化合物组合物，用于基因调控的RNA干扰途径。这些经过修饰的寡核苷酸化合物包括至少具有一种亲和力修饰的siRNA和asRNA。
• OLIGOMERIC COMPOUNDS COMPRISING 4'-THIONUCLEOSIDES FOR USE IN GENE MODULATION
  申请人：Bhat Balkrishen

  公开号：US20100324277A1

  公开（公告）日：2010-12-23

  The present invention provides modified oligomeric compounds and compositions of oligomeric compounds for use in the RNA interference pathway of gene modulation. The modified oligomeric compounds include siRNA and asRNA having at least one affinity modification.

  本发明提供了修改的寡核苷酸化合物和寡核苷酸化合物组合物，用于基因调节的RNA干扰途径。修改的寡核苷酸化合物包括至少具有一种亲和力修饰的siRNA和asRNA。
• [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.
• 4'-THIONUCLEOSIDES AND OLIGOMERIC COMPOUNDS
  申请人：Isis Pharmaceuticals, Inc.

  公开号：EP1677822B1

  公开（公告）日：2014-04-23