[(2R,3S,5R)-5-[2,4-dioxo-5-[2-(6-pent-1-ynylpyridin-3-yl)ethynyl]pyrimidin-1-yl]-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate | 948560-07-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: [(2R,3S,5R)-5-[2,4-dioxo-5-[2-(6-pent-1-ynylpyridin-3-yl)ethynyl]pyrimidin-1-yl]-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
• CAS: 948560-07-4
• 化学式: C₃₇H₃₃N₃O₇
• 分子量: 631.685
• InChiKey: IWWBXBQTQQXSAS-WIHCDAFUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(2R,3S,5R)-5-[2,4-dioxo-5-[2-(6-pent-1-ynylpyridin-3-yl)ethynyl]pyrimidin-1-yl]-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate 在 氢氧化钾 、 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(6-pent-1-ynylpyridin-3-yl)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：

  2-(1-pentynyl)-5-bromopyridine 在 copper(l) iodide 、 四(三苯基膦)钯 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 生成 [(2R,3S,5R)-5-[2,4-dioxo-5-[2-(6-pent-1-ynylpyridin-3-yl)ethynyl]pyrimidin-1-yl]-3-(4-methylbenzoyl)oxyoxolan-2-yl]methyl 4-methylbenzoate
  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

文献信息

• Synthesis and Antiviral Evaluation of 6-(Alkyl-heteroaryl)furo[2,3-<i>d</i>]pyrimidin-2(3<i>H</i>)-one Nucleosides and Analogues with Ethynyl, Ethenyl, and Ethyl Spacers at C6 of the Furopyrimidine Core
  作者：Morris J. Robins、Ireneusz Nowak、Vivek K. Rajwanshi、Karl Miranda、John F. Cannon、Matt A. Peterson、Graciela Andrei、Robert Snoeck、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm070210n

  日期：2007.8.1

  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.