2-bromo-4,5-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazole | 801303-82-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 咪唑核糖核苷和核糖核苷酸
• 英文名称: 2-bromo-4,5-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazole
• 英文别名: [(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(2-bromo-4,5-dichloroimidazol-1-yl)oxolan-2-yl]methyl benzoate
• CAS: 801303-82-2
• 化学式: C₂₉H₂₁BrCl₂N₂O₇
• 分子量: 660.305
• InChiKey: VMUCQQRBCRHXMI-NMOFPLQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-bromo-4,5-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazole 在 三苯基膦 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 24.0h， 以71%的产率得到4,5-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Polyhalogenated Imidazole Nucleosides:  Dimensional Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole

  摘要：

  A series of polyhalogenated imidazole nucleosides were designed and synthesized as ring-contracted analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and its 2-bromo analogue (BDCRB) in an effort to explore the spatial limitation of the active pocket(s) in the target protein(s). 2,4,5-Trichloro-, 2-bromo-4,5-dichloro-, and 2,4,5-tribromoimidazole nucleosides were prepared by a condensation of the preformed heterocycles with the appropriate sugar precursors. The ribofuranosyl and xylofuranosyl analogues were prepared by a direct glycosylation using the Vorbruggen's silylation method and provided exclusively the beta-anomers. The arabinofuranosyl analogues were prepared by the sodium salt method to give both the alpha-and beta-anomers. The absolute configurations were established by H-1 NMR spectroscopy. Alkylation of the polyhalogenated imidazoles with the appropriate bromomethyl ethers gave the acyclic acyclovir and ganciclovir analogues. In general, the parent polyhalogenated imidazoles showed some activity against human cytomegalovirus (HCMV) (IC50 similar to 35 muM). However, with the exception of two tribromo analogues (7c, 13c-beta), most of their nucleoside derivatives were inactive against both HCMW and herpes simplex virus type-1 (HSV-1) and were not cytotoxic. The results suggest that the ring-contracted nucleoside analogues of TCRB and BDCRB interacted weakly or not at all with viral and cellular targets.

  DOI：

  10.1021/jm040016q
• 作为产物：
  描述：

  1-乙酰氧基-2,3,5-三苯甲酰氧基-1-beta-D-呋喃核糖 、 2-溴-4,5-二氯咪唑 在 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙腈 为溶剂， 以92%的产率得到2-bromo-4,5-dichloro-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)imidazole
  参考文献：
  名称：

  Synthesis and Antiviral Evaluation of Polyhalogenated Imidazole Nucleosides:  Dimensional Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole

  摘要：

  A series of polyhalogenated imidazole nucleosides were designed and synthesized as ring-contracted analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and its 2-bromo analogue (BDCRB) in an effort to explore the spatial limitation of the active pocket(s) in the target protein(s). 2,4,5-Trichloro-, 2-bromo-4,5-dichloro-, and 2,4,5-tribromoimidazole nucleosides were prepared by a condensation of the preformed heterocycles with the appropriate sugar precursors. The ribofuranosyl and xylofuranosyl analogues were prepared by a direct glycosylation using the Vorbruggen's silylation method and provided exclusively the beta-anomers. The arabinofuranosyl analogues were prepared by the sodium salt method to give both the alpha-and beta-anomers. The absolute configurations were established by H-1 NMR spectroscopy. Alkylation of the polyhalogenated imidazoles with the appropriate bromomethyl ethers gave the acyclic acyclovir and ganciclovir analogues. In general, the parent polyhalogenated imidazoles showed some activity against human cytomegalovirus (HCMV) (IC50 similar to 35 muM). However, with the exception of two tribromo analogues (7c, 13c-beta), most of their nucleoside derivatives were inactive against both HCMW and herpes simplex virus type-1 (HSV-1) and were not cytotoxic. The results suggest that the ring-contracted nucleoside analogues of TCRB and BDCRB interacted weakly or not at all with viral and cellular targets.

  DOI：

  10.1021/jm040016q

文献信息

• Synthesis and Antiviral Evaluation of Polyhalogenated Imidazole Nucleosides:  Dimensional Analogues of 2,5,6-Trichloro-1-(β-<scp>d</scp>-ribofuranosyl)benzimidazole
  作者：Tun-Cheng Chien、Sunita S. Saluja、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm040016q

  日期：2004.11.1

  A series of polyhalogenated imidazole nucleosides were designed and synthesized as ring-contracted analogues of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and its 2-bromo analogue (BDCRB) in an effort to explore the spatial limitation of the active pocket(s) in the target protein(s). 2,4,5-Trichloro-, 2-bromo-4,5-dichloro-, and 2,4,5-tribromoimidazole nucleosides were prepared by a condensation of the preformed heterocycles with the appropriate sugar precursors. The ribofuranosyl and xylofuranosyl analogues were prepared by a direct glycosylation using the Vorbruggen's silylation method and provided exclusively the beta-anomers. The arabinofuranosyl analogues were prepared by the sodium salt method to give both the alpha-and beta-anomers. The absolute configurations were established by H-1 NMR spectroscopy. Alkylation of the polyhalogenated imidazoles with the appropriate bromomethyl ethers gave the acyclic acyclovir and ganciclovir analogues. In general, the parent polyhalogenated imidazoles showed some activity against human cytomegalovirus (HCMV) (IC50 similar to 35 muM). However, with the exception of two tribromo analogues (7c, 13c-beta), most of their nucleoside derivatives were inactive against both HCMW and herpes simplex virus type-1 (HSV-1) and were not cytotoxic. The results suggest that the ring-contracted nucleoside analogues of TCRB and BDCRB interacted weakly or not at all with viral and cellular targets.