1-(5-amino-2,5-dideoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine | 105281-13-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 英文名称: 1-(5-amino-2,5-dideoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine
• 英文别名: 1-(5-amino-2,5-dideoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine；4-amino-1-[(2R,3S,4R,5R)-5-(aminomethyl)-3-fluoro-4-hydroxyoxolan-2-yl]-5-iodopyrimidin-2-one
• CAS: 105281-13-8
• 化学式: C₉H₁₂FIN₄O₃
• 分子量: 370.122
• InChiKey: PLTHDZDHDMWBBR-BYPJNBLXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  非西他滨 在 吡啶 、 叠氮化锂 、 三苯基膦 作用下， 以 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 1-(5-amino-2,5-dideoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine
  参考文献：
  名称：

  Nucleosides. 139. Synthesis and anticytomegalovirus and antiherpes simplex virus activity of 5'-modified analogs of 2'-fluoroarabinosylpyrimidine nucleosides

  摘要：

  In order to determine if modification of the 5'-position reduces or abolishes the antiviral activity of 2'-fluoro-5-iodo-ara-C (FIAC), 2'-fluoro-5-iodo-ara-U (FIAU), or 2'-fluoro-5-methyl-ara-U (FMAU) against human cytomegalovirus (HCMV) and herpes simplex virus (HSV), the 5'-deoxy, 5'-mercapto, and 5'-amino analogues of these nucleosides were prepared. 5'-Deoxy-FIAC and 5'-deoxy-FIAU were prepared by catalytic hydrogenation of 5'-iodo-FIAC and 5'-iodo-FIAU to 5'-deoxy-FAC and 5'-deoxy-FAU, respectively, followed by reiodination at C-5. Reduction of 5'-iodo-FMAU afforded 5'-deoxy-FMAU. These 5'-deoxy nucleosides were found to be inactive against HCMV, indicating that the conversion to 5'-phosphate by the cellular enzyme(s) is a requirement for antiviral activity against this virus. Other 5'-modified (NH2 and SH) analogues were also prepared from 5'-O-tosyl-FIAC and 5'-O-tosyl-FMAU. Treatment of these tosylates with LiN3 in DMF afforded the corresponding 5'-N3 products. Catalytic hydrogenation of 5'-N3-FMAU afforded 5'-NH2-FMAU, whereas 5'-NH2-FIAC was obtained by treatment of 5'-N3-FIAC with Ph3P in pyridine. 5'-Mercapto analogues were prepared by treatment of 5'-O-tosyl-3'-O-acetyl nucleosides with KSAc followed by deacetylation. 5'-NH2-FMAU was the only compound that showed good activity against HSV-1 and HSV-2 in vitro. However, this compound was less potent and had a lower therapeutic index than FMAU.

  DOI：

  10.1021/jm00384a041

文献信息

• Nucleosides. 139. Synthesis and anticytomegalovirus and antiherpes simplex virus activity of 5'-modified analogs of 2'-fluoroarabinosylpyrimidine nucleosides
  作者：Kazuho Harada、Jasenka Matulic-Adamic、Richard W. Price、Raymond F. Schinazi、Kyoichi A. Watanabe、Jack J. Fox

  DOI：10.1021/jm00384a041

  日期：1987.1

  In order to determine if modification of the 5'-position reduces or abolishes the antiviral activity of 2'-fluoro-5-iodo-ara-C (FIAC), 2'-fluoro-5-iodo-ara-U (FIAU), or 2'-fluoro-5-methyl-ara-U (FMAU) against human cytomegalovirus (HCMV) and herpes simplex virus (HSV), the 5'-deoxy, 5'-mercapto, and 5'-amino analogues of these nucleosides were prepared. 5'-Deoxy-FIAC and 5'-deoxy-FIAU were prepared by catalytic hydrogenation of 5'-iodo-FIAC and 5'-iodo-FIAU to 5'-deoxy-FAC and 5'-deoxy-FAU, respectively, followed by reiodination at C-5. Reduction of 5'-iodo-FMAU afforded 5'-deoxy-FMAU. These 5'-deoxy nucleosides were found to be inactive against HCMV, indicating that the conversion to 5'-phosphate by the cellular enzyme(s) is a requirement for antiviral activity against this virus. Other 5'-modified (NH2 and SH) analogues were also prepared from 5'-O-tosyl-FIAC and 5'-O-tosyl-FMAU. Treatment of these tosylates with LiN3 in DMF afforded the corresponding 5'-N3 products. Catalytic hydrogenation of 5'-N3-FMAU afforded 5'-NH2-FMAU, whereas 5'-NH2-FIAC was obtained by treatment of 5'-N3-FIAC with Ph3P in pyridine. 5'-Mercapto analogues were prepared by treatment of 5'-O-tosyl-3'-O-acetyl nucleosides with KSAc followed by deacetylation. 5'-NH2-FMAU was the only compound that showed good activity against HSV-1 and HSV-2 in vitro. However, this compound was less potent and had a lower therapeutic index than FMAU.