9-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)adenine | 306305-05-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 9-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)adenine
• 英文别名: 3',5'-di-O-benzyl-4'-C-triethylsilylethynyladenosine；(2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-4-phenylmethoxy-5-(phenylmethoxymethyl)-5-(2-triethylsilylethynyl)oxolan-3-ol
• CAS: 306305-05-5
• 化学式: C₃₂H₃₉N₅O₄Si
• 分子量: 585.778
• InChiKey: ADIWHKYYMHUCJC-SEISLXRGSA-N

物化性质

• 熔点：
  105-108 °C
• 沸点：
  738.3±70.0 °C(predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)adenine 在 4-二甲氨基吡啶 、 偶氮二异丁腈 、 四丁基氟化铵 、 氨 、 三正丁基氢锡 、 sodium 作用下， 以 四氢呋喃 、 甲苯 、 乙腈 为溶剂， 反应 2.67h， 生成 (2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-2-ethynyl-2-(hydroxymethyl)tetrahydrofuran-3-ol
  参考文献：
  名称：

  Syntheses of 4‘-C-Ethynyl-β-d-arabino- and 4‘-C-Ethynyl-2‘-deoxy-β-d-ribo-pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity

  摘要：

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.

  DOI：

  10.1021/jm000209n
• 作为产物：
  描述：

  9-(2-O-acetyl-3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)adenine 以 甲醇 、 三乙胺 为溶剂， 反应 24.0h， 生成 9-(3,5-di-O-benzyl-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)adenine
  参考文献：
  名称：

  4′-C-ethynyl pyrimidine nucleosides and pharmaceutical compositions thereof

  摘要：

  本发明提供了4'-C-乙炔基嘧啶核苷（不包括4'-C-乙炔基胸腺嘧啶）的化合物，其化学式表示为[I]：其中B代表从嘧啶和其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。

  公开号：

  US06403568B1

文献信息

• 4′-C-ethynyl pyrimidine nucleoside compounds and pharmaceutical compositions
  申请人：Yamasa Corporation

  公开号：US06291670B1

  公开（公告）日：2001-09-18

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  该发明提供了由公式[I]表示的4'-C-乙炔嘧啶核苷（除了4'-C-乙炔胸腺嘧啶）：其中B代表从嘧啶及其衍生物组成的基；X代表氢原子或羟基；R代表氢原子或磷酸酯基团；以及含有任一化合物和药学上可接受的载体的药物组合物。最好，该组合物用作抗HIV药剂或治疗艾滋病的药物。
• 4'-C-ethynyl pyrimidine nucleoside compounds
  申请人：——

  公开号：US20020022722A1

  公开（公告）日：2002-02-21

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: 1 wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  本发明提供了4'-C-乙炔基嘧啶核苷（不包括4'-C-乙炔基胸腺嘧啶）的化合物，其化学式为[I]：其中B代表从嘧啶和其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有上述任一化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4′-C-ethynyl pyrimidine nucleosides and pharmaceutical compositions thereof
  申请人：Yamasa Corporation

  公开号：US06403568B1

  公开（公告）日：2002-06-11

  The invention provides 4′-C-ethynyl pyrimidine nucleosides (other than 4′-C-ethynylthymidine) represented by formula [I]: wherein B represents a base selected from the group consisting of pyrimidine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  本发明提供了4'-C-乙炔基嘧啶核苷（不包括4'-C-乙炔基胸腺嘧啶）的化合物，其化学式表示为[I]：其中B代表从嘧啶和其衍生物中选择的碱基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• 4′-C-ethynyl purine nucleoside compounds
  申请人：Yamasa Corporation

  公开号：US06333315B1

  公开（公告）日：2001-12-25

  The invention provides 4′-C-ethynyl purine nucleosides represented by formula [I]: wherein B represents a base selected from the group consisting of purine and derivatives thereof; X represents a hydrogen atom or a hydroxyl group; and R represents a hydrogen atom or a phosphate residue; and a pharmaceutical composition containing any one of the compounds and a pharmaceutically acceptable carrier. Preferably, the composition is used as an anti-HIV agent or a drug for treating AIDS.

  该发明提供了由公式[I]所表示的4'-C-乙炔基嘌呤核苷，其中B代表从嘌呤及其衍生物组成的基；X代表氢原子或羟基；R代表氢原子或磷酸残基；以及含有任何一种化合物和药学上可接受的载体的制药组合物。优选地，该组合物用作抗HIV剂或治疗艾滋病的药物。
• Syntheses of 4<i>‘</i><i>-</i><i>C</i>-Ethynyl-β-<scp>d</scp>-<i>arabino- </i>and 4‘-<i>C-</i>Ethynyl-2<i>‘</i>-deoxy-β-<scp>d</scp>-<i>ribo-</i>pentofuranosylpyrimidines and -purines and Evaluation of Their Anti-HIV Activity
  作者：Hiroshi Ohrui、Satoru Kohgo、Kenji Kitano、Shinji Sakata、Eiichi Kodama、Kazuhisa Yoshimura、Masao Matsuoka、Shiro Shigeta、Hiroaki Mitsuya

  DOI：10.1021/jm000209n

  日期：2000.11.1

  4'-C-Ethynyl-beta -D-arabino- and 4'-C-ethynyl-2'-deoxy-beta -D-ribo-pentofuranosylpyrine and -purine nucleosides were synthesized and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl- or 4-C-triethylsilylethynyl-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O-2,2'-anhydro nucleosides. The 2'-deoxy-ribo derivatives were synthesized by radical reduction of 2'-bromo or 2'- phenoxythiocarbonyloxy nucleosides. Among these 4'-C-ethynyl nucleosides, seven analogues proved to be potent against HIV-1 in vitro with EC50 values ranging from 0.0003 to 0.03 muM. These compounds also exerted activity against clinical and multi-dideoxy-nucleoside-resistant HIV-1 strains with comparable EC50 values. Three such 4'-C-ethynyl-2'-deoxypurine analogues including 4'-C-ethynyl-2'-deoxyadenosine and 4'-C-ethynyl-2,6-diamino-2'-deoxy-purine were less cytotoxic [selectivity indices (SIs): 975-2733] than three 4'-C-ethynyl-2-deoxycytidine analogues (SIs: 63-363). 4'-C-Ethynyl-5-fluoro-2'-deoxycytidine was least toxic (SI: >3333) and potent against all HIV strains tested.