Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-(5-chloro-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-2-triethylsilanylethynyl-tetrahydro-furan-3-yl ester | 1055039-78-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-(5-chloro-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-2-triethylsilanylethynyl-tetrahydro-furan-3-yl ester
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-[5-chloro-2-oxo-4-(1,2,4-triazol-1-yl)pyrimidin-1-yl]-2-(2-triethylsilylethynyl)oxolan-2-yl]methyl acetate
• CAS: 1055039-78-5
• 化学式: C₂₃H₃₀ClN₅O₆Si
• 分子量: 536.06
• InChiKey: YFIATHHTFYGSKB-MIZPHKNDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.68
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-(5-chloro-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-2-triethylsilanylethynyl-tetrahydro-furan-3-yl ester 在 25percent aq. ammonium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 4-Amino-5-chloro-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-5-triethylsilanylethynyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one
  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：

  1-(3,5-di-O-acetyl-2-deoxy-4-C-triethylsilylethynyl-β-D-ribo-pentofuranosyl)uracil 在 吡啶 、 ammonium cerium(IV) nitrate 、 溶剂黄146 、 lithium chloride 、 4-氯苯基二氯磷酸酯 作用下， 以 乙腈 为溶剂， 反应 174.08h， 生成 Acetic acid (2R,3S,5R)-2-acetoxymethyl-5-(5-chloro-2-oxo-4-[1,2,4]triazol-1-yl-2H-pyrimidin-1-yl)-2-triethylsilanylethynyl-tetrahydro-furan-3-yl ester
  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