2,5,6-trichloro-1-(2,3-di-O-acetyl-5-chloro-5-deoxy-β-D-ribofuranosyl)benzimidazole | 185453-60-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,5,6-trichloro-1-(2,3-di-O-acetyl-5-chloro-5-deoxy-β-D-ribofuranosyl)benzimidazole
• 英文别名: Acetic acid, 4-acetoxy-2-chloromethyl-5-(2,5,6-trichloro-benzoimidazol-1-yl)-tetrahydro-furan-3-yl ester；[(2S,3S,4R,5R)-4-acetyloxy-2-(chloromethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolan-3-yl] acetate
• CAS: 185453-60-5
• 化学式: C₁₆H₁₄Cl₄N₂O₅
• 分子量: 456.11
• InChiKey: FSUCSZKGFXRWKL-KBUPBQIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,5,6-trichloro-1-(2,3-di-O-acetyl-5-chloro-5-deoxy-β-D-ribofuranosyl)benzimidazole 在 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以75%的产率得到2,5,6-trichloro-1-(5-chloro-5-deoxy-β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Certain 5‘-Modified Analogs of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole

  摘要：

  A series of 5'-modified 2,5,6-trichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpesviruses and for cytotoxicity. The 5'-methoxy, 5'-ethoxy, and 5'-butoxy analogs of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were prepared by coupling the appropriate 5-O-alkyl-1,2,3-tri-O-acetyl-beta-D-ribose derivatives with 2,5,6-trichlorobenzimidazole followed by removal of the protecting groups. The 5'-deoxy-5'-fluoro, -5'-chloro, -5'-bromo, -5'-iodo, -5'-azido, and -5'-thiomethyl derivatives were synthesized in a similar fashion. All of these 5'-modified derivatives had significant activity against HCMV in plaque and yield reduction assays (IC50's = 0.5-14.2 mu M) but had little activity (IC50's > 100 mu M) against HSV-1. This pattern is similar to the antiviral activity profile observed for TCRB. The 5'-halogenated derivatives were more active than the other 5'-modified derivatives with antiviral activity well separated from cytotoxicity. In general, cytotoxicity of all the 5'-modified derivatives was greater in human foreskin fibroblasts (HFF cells) than in L1210 or K-B tumor cells. These results indicate that the viral target tolerates significant modifications of TCRB at the 5'-position without adversely affecting activity against HCMV, whereas the 5'-modifications increased cytotoxicity in human diploid cells.

  DOI：

  10.1021/jm9604888
• 作为产物：
  描述：

  卡培他滨中间体 在 吡啶 、 盐酸 、 三氟甲磺酸三甲基硅酯 、 牛血清白蛋白 作用下， 反应 26.75h， 生成 2,5,6-trichloro-1-(2,3-di-O-acetyl-5-chloro-5-deoxy-β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis and Antiviral Activity of Certain 5‘-Modified Analogs of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole

  摘要：

  A series of 5'-modified 2,5,6-trichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpesviruses and for cytotoxicity. The 5'-methoxy, 5'-ethoxy, and 5'-butoxy analogs of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were prepared by coupling the appropriate 5-O-alkyl-1,2,3-tri-O-acetyl-beta-D-ribose derivatives with 2,5,6-trichlorobenzimidazole followed by removal of the protecting groups. The 5'-deoxy-5'-fluoro, -5'-chloro, -5'-bromo, -5'-iodo, -5'-azido, and -5'-thiomethyl derivatives were synthesized in a similar fashion. All of these 5'-modified derivatives had significant activity against HCMV in plaque and yield reduction assays (IC50's = 0.5-14.2 mu M) but had little activity (IC50's > 100 mu M) against HSV-1. This pattern is similar to the antiviral activity profile observed for TCRB. The 5'-halogenated derivatives were more active than the other 5'-modified derivatives with antiviral activity well separated from cytotoxicity. In general, cytotoxicity of all the 5'-modified derivatives was greater in human foreskin fibroblasts (HFF cells) than in L1210 or K-B tumor cells. These results indicate that the viral target tolerates significant modifications of TCRB at the 5'-position without adversely affecting activity against HCMV, whereas the 5'-modifications increased cytotoxicity in human diploid cells.

  DOI：

  10.1021/jm9604888

文献信息

• Synthesis and Antiviral Activity of Certain 5‘-Modified Analogs of 2,5,6-Trichloro-1-(β-<scp>d</scp>-ribofuranosyl)benzimidazole
  作者：Kristjan S. Gudmundsson、John C. Drach、Linda L. Wotring、Leroy B. Townsend

  DOI：10.1021/jm9604888

  日期：1997.2.1

  A series of 5'-modified 2,5,6-trichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpesviruses and for cytotoxicity. The 5'-methoxy, 5'-ethoxy, and 5'-butoxy analogs of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were prepared by coupling the appropriate 5-O-alkyl-1,2,3-tri-O-acetyl-beta-D-ribose derivatives with 2,5,6-trichlorobenzimidazole followed by removal of the protecting groups. The 5'-deoxy-5'-fluoro, -5'-chloro, -5'-bromo, -5'-iodo, -5'-azido, and -5'-thiomethyl derivatives were synthesized in a similar fashion. All of these 5'-modified derivatives had significant activity against HCMV in plaque and yield reduction assays (IC50's = 0.5-14.2 mu M) but had little activity (IC50's > 100 mu M) against HSV-1. This pattern is similar to the antiviral activity profile observed for TCRB. The 5'-halogenated derivatives were more active than the other 5'-modified derivatives with antiviral activity well separated from cytotoxicity. In general, cytotoxicity of all the 5'-modified derivatives was greater in human foreskin fibroblasts (HFF cells) than in L1210 or K-B tumor cells. These results indicate that the viral target tolerates significant modifications of TCRB at the 5'-position without adversely affecting activity against HCMV, whereas the 5'-modifications increased cytotoxicity in human diploid cells.