[(3aR,4R,6R,6aR)-2,2-Dimethyl-6-(2,5,6-trichloro-benzoimidazol-1-yl)-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol | 185453-53-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 苯并咪唑核糖核苷和核糖核苷酸
• 英文名称: [(3aR,4R,6R,6aR)-2,2-Dimethyl-6-(2,5,6-trichloro-benzoimidazol-1-yl)-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol
• 英文别名: [(3aR,4R,6R,6aR)-2,2-dimethyl-4-(2,5,6-trichlorobenzimidazol-1-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 185453-53-6
• 化学式: C₁₅H₁₅Cl₃N₂O₄
• 分子量: 393.654
• InChiKey: BWMMCZIIJUGLPE-FDYHWXHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  65.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(3aR,4R,6R,6aR)-2,2-Dimethyl-6-(2,5,6-trichloro-benzoimidazol-1-yl)-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol 在 叠氮磷酸二苯酯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 生成 1-((3aR,4R,6R,6aR)-6-Azidomethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-2,5,6-trichloro-1H-benzoimidazole
  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：

  2,2-二甲氧基丙烷 、 2,5,6-trichloro-1-β-D-ribofuranosyl-1H-benzimidazole 在 Dowex 50 (H⁺) 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以73%的产率得到[(3aR,4R,6R,6aR)-2,2-Dimethyl-6-(2,5,6-trichloro-benzoimidazol-1-yl)-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol
  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

• 5'-substituted-ribofuranosyl benzimidazoles as antiviral agents
  申请人：——

  公开号：US20030119762A1

  公开（公告）日：2003-06-26

  The present invention relates to polysubstituted benzimidazoles, having the following formula: 1 wherein Q is a substituted benzimidazole group attached at the benzimidazole 1-position; R is a halogen of atomic number 9 to 53, inclusive (i.e., —F, —Cl, —Br, or —I); azido (i.e., —N 3 ); or —X—R 1 , wherein X is a chalcogen of atomic number 8 to 16, inclusive (i.e., —O— or —S—), and R 1 may be straight or branched chain alkyl of 1 to 8 carbon atoms; and R 2 and R 3 may be the same or different and are separately —O—C(═O)CH 3 (i.e., —OAc) or hydroxy (i.e., —OH); and pharmaceutically acceptable salts and operative combinations thereof. Also provided by this invention are compositions comprising a polysubstituted benzimidazole as defined above and methods of use thereof.

  本发明涉及具有下式的多取代苯并咪唑： 1 其中 Q 是连接在苯并咪唑 1 位上的取代苯并咪唑基团；R 是原子序数为 9 至 53（含）的卤素（即 -F、-Cl、-Br 或 -I）；叠氮（即 -N 3 ）；或 -X-R 1 其中 X 是原子序数为 8 至 16（包括 8 和 16）的缩醛（即 -O- 或 -S-），而 R 1 可以是 1 至 8 个碳原子的直链或支链烷基；以及 R 2 和 R 3 可以相同或不同，并分别为-O-C(═O)CH 3 (即-OAc)或羟基(即-OH)；以及药学上可接受的盐及其作用组合。本发明还提供了包含如上定义的多取代苯并咪唑的组合物及其使用方法。
• 5'-SUBSTITUTED-RIBOFURANOSYL BENZIMIDAZOLES AS ANTIVIRAL AGENTS
  申请人：The Regents of The University of Michigan

  公开号：EP0845001B1

  公开（公告）日：2002-11-13
• US5874413A
  申请人：——

  公开号：US5874413A

  公开（公告）日：1999-02-23
• 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.