5,6-dichloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazol-2-one | 149622-95-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 5,6-dichloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazol-2-one
• 英文别名: [(2R,3R,4R,5R)-3,4-diacetyloxy-5-(5,6-dichloro-2-oxo-3H-benzimidazol-1-yl)oxolan-2-yl]methyl acetate
• CAS: 149622-95-7
• 化学式: C₁₈H₁₈Cl₂N₂O₈
• 分子量: 461.256
• InChiKey: PFDRREJTYUKVFK-QBPKDAKJSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5,6-dichloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazol-2-one 在 亚硝酸特丁酯 、 二碘甲烷 作用下， 反应 2.0h， 生成 5,6-dichloro-4-nitro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazol-2-one
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Certain 2,5,6-Trihalo-1-(.beta.-D-ribofuranosyl)benzimidazoles

  摘要：

  A new series of 2-substituted 5,6-dichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpes viruses and for cytotoxicity. 2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) was prepared by ribosylation of the heterocycle 2,5,6-trichlorobenzimidazole followed by a removal of the protecting groups. The 2-bromo derivative (BDCRB) was made in a similar fashion from 2-bromo-5,6-dichlorobenzimidazole. In contrast, the 2-iodo derivative presented a more difficult problem since the appropriate heterocycle was unavailable. This prompted us to prepare the 2-amino derivative followed by nonaqueous diazotization and removal of the blocking groups. Biological evaluation revealed marked differences in the activities of these compounds and the closely related known compound 5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB). DRB was weakly active against both human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), (IC50's = 42 and 30 mu M, respectively) but-was cytotoxic to uninfected human foreskin fibroblasts and KB cells in the same dose range. Similar results were obtained with the heterocycle 2,5,6-trichlorobenzimidazole. In marked contrast, the ribonucleoside of 2,5,6-trichlorobenzimidazole (TCRB) was active against HCMV (IC50 = 2.9 mu M, plaque assay; IC50 = 1.4 mu M, yield assay) but only weakly active against HSV-1 (IC50 = 102 mu M, plaque assay). Little to no cytotoxicity was observed in HFF and KB cells at concentrations up to 100 mu M. By changing the substituent at the 2-position from chlorine to bromine (BDCRB), a 4-fold increase in activity against HCMV was observed without any significant increase in cytotoxicity. In contrast, the 2-I and 2-NH2 derivatives were only weakly active against HCMV and HSV-1 with activity not well-separated from cytotoxicity. These data establish that for maximum activity against HCMV with separation from cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is apparently preferred at the 2-position. The activity and selectivity of both TCRB and BDCRB were better than that observed with either ganciclovir or foscarnet.

  DOI：

  10.1021/jm00020a025
• 作为产物：
  描述：

  5,6-二氯-1H-苯并[d]咪唑-2(3H)-酮 在 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 反应 1.08h， 生成 5,6-dichloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazol-2-one
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Certain 2,5,6-Trihalo-1-(.beta.-D-ribofuranosyl)benzimidazoles

  摘要：

  A new series of 2-substituted 5,6-dichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpes viruses and for cytotoxicity. 2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) was prepared by ribosylation of the heterocycle 2,5,6-trichlorobenzimidazole followed by a removal of the protecting groups. The 2-bromo derivative (BDCRB) was made in a similar fashion from 2-bromo-5,6-dichlorobenzimidazole. In contrast, the 2-iodo derivative presented a more difficult problem since the appropriate heterocycle was unavailable. This prompted us to prepare the 2-amino derivative followed by nonaqueous diazotization and removal of the blocking groups. Biological evaluation revealed marked differences in the activities of these compounds and the closely related known compound 5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB). DRB was weakly active against both human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), (IC50's = 42 and 30 mu M, respectively) but-was cytotoxic to uninfected human foreskin fibroblasts and KB cells in the same dose range. Similar results were obtained with the heterocycle 2,5,6-trichlorobenzimidazole. In marked contrast, the ribonucleoside of 2,5,6-trichlorobenzimidazole (TCRB) was active against HCMV (IC50 = 2.9 mu M, plaque assay; IC50 = 1.4 mu M, yield assay) but only weakly active against HSV-1 (IC50 = 102 mu M, plaque assay). Little to no cytotoxicity was observed in HFF and KB cells at concentrations up to 100 mu M. By changing the substituent at the 2-position from chlorine to bromine (BDCRB), a 4-fold increase in activity against HCMV was observed without any significant increase in cytotoxicity. In contrast, the 2-I and 2-NH2 derivatives were only weakly active against HCMV and HSV-1 with activity not well-separated from cytotoxicity. These data establish that for maximum activity against HCMV with separation from cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is apparently preferred at the 2-position. The activity and selectivity of both TCRB and BDCRB were better than that observed with either ganciclovir or foscarnet.

  DOI：

  10.1021/jm00020a025