3-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-[(4-methylphenyl)ethynyl]furo[2,3-d]pyrimidin-2(3H)-one | 948559-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃[2,3-d]嘧啶
• 英文名称: 3-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-[(4-methylphenyl)ethynyl]furo[2,3-d]pyrimidin-2(3H)-one
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-[6-[2-(4-methylphenyl)ethynyl]-2-oxofuro[2,3-d]pyrimidin-3-yl]oxolan-2-yl]methyl acetate
• CAS: 948559-76-0
• 化学式: C₂₄H₂₂N₂O₇
• 分子量: 450.448
• InChiKey: MZGAXWBLVAYRRV-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-[(4-methylphenyl)ethynyl]furo[2,3-d]pyrimidin-2(3H)-one 在 palladium on activated charcoal 氨 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 7.5h， 生成 3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[2-(4-methylphenyl)ethyl]furo[2,3-d]pyrimidin-2-one
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of 6-(Alkyl-heteroaryl)furo[2,3-d]pyrimidin-2(3H)-one Nucleosides and Analogues with Ethynyl, Ethenyl, and Ethyl Spacers at C6 of the Furopyrimidine Core

  摘要：

  Sonogashira coupling strategies were employed to synthesize new furo[2,3-d]pyrimidin-2(3H)-one (FuPyrm) 2'-deoxynucleoside analogues. Partial or complete reduction of ethyne-linked compounds afforded ethenyl-and ethyl-linked derivatives. Levels of inhibition of varicella-zoster virus (VZV), human cytomegalovirus (HCMV), a broad range of other DNA and RNA viruses, and several cancer cell lines were evaluated in cell cultures. The anti-VZV potency decreased with increasing rigidity of the side chain at C6 of the FuPyrm ring in the order dec-1-yn-1-yl < dec-1-en-1-yl < decan-1-yl. In contrast, compounds with a rigid ethynyl spacer between C6 of the FuPyrm ring and a 4-alkylphenyl moiety were more potent inhibitors of VZV than the corresponding derivatives with an ethyl spacer. Replacement of the phenyl moiety in 6-(4-alkylphenyl) derivatives with a pyridine ring (in either regioisomeric orientation) gave analogues with increased solubility in methanol but reduced anti-VZV potency, and replacement with a pyrimidine ring reduced the anti-VZV activity even further. The pyridine-ring-containing analogues were similar to 20-fold more potent inhibitors of VZV than acyclovir but were similar to 6-fold less potent than BVDU and similar to 60-fold weaker than the most active 6-(4-pentylphenyl) -substituted prototype.

  DOI：

  10.1021/jm070210n
• 作为产物：
  描述：

  3-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-bromofuro[2,3-d]pyrimidin-2(3H)-one 、 4-甲苯基乙炔 在 copper(l) iodide 、 四(三苯基膦)钯 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以54%的产率得到3-(3,5-di-O-acetyl-2-deoxy-β-D-erythro-pentofuranosyl)-6-[(4-methylphenyl)ethynyl]furo[2,3-d]pyrimidin-2(3H)-one
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of 6-(Alkyl-heteroaryl)furo[2,3-d]pyrimidin-2(3H)-one Nucleosides and Analogues with Ethynyl, Ethenyl, and Ethyl Spacers at C6 of the Furopyrimidine Core

  摘要：

  Sonogashira coupling strategies were employed to synthesize new furo[2,3-d]pyrimidin-2(3H)-one (FuPyrm) 2'-deoxynucleoside analogues. Partial or complete reduction of ethyne-linked compounds afforded ethenyl-and ethyl-linked derivatives. Levels of inhibition of varicella-zoster virus (VZV), human cytomegalovirus (HCMV), a broad range of other DNA and RNA viruses, and several cancer cell lines were evaluated in cell cultures. The anti-VZV potency decreased with increasing rigidity of the side chain at C6 of the FuPyrm ring in the order dec-1-yn-1-yl < dec-1-en-1-yl < decan-1-yl. In contrast, compounds with a rigid ethynyl spacer between C6 of the FuPyrm ring and a 4-alkylphenyl moiety were more potent inhibitors of VZV than the corresponding derivatives with an ethyl spacer. Replacement of the phenyl moiety in 6-(4-alkylphenyl) derivatives with a pyridine ring (in either regioisomeric orientation) gave analogues with increased solubility in methanol but reduced anti-VZV potency, and replacement with a pyrimidine ring reduced the anti-VZV activity even further. The pyridine-ring-containing analogues were similar to 20-fold more potent inhibitors of VZV than acyclovir but were similar to 6-fold less potent than BVDU and similar to 60-fold weaker than the most active 6-(4-pentylphenyl) -substituted prototype.

  DOI：

  10.1021/jm070210n