2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole | 142371-80-0

• 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: 2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole
• 英文别名: 2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazole；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(2-chloro-5,6-difluorobenzimidazol-1-yl)oxolan-2-yl]methyl acetate
• CAS: 142371-80-0
• 化学式: C₁₈H₁₇ClF₂N₂O₇
• 分子量: 446.792
• InChiKey: VUKRJEXHOOPPFI-QBPKDAKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  106
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole 在 甲醇 作用下， 以 ammonia methanol 为溶剂， 反应 3.0h， 以to give 0.573 g (3 crops, 89%) of 65 as a crystalline compound的产率得到2-chloro-5,6-difluoro-1-(β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Treatment of herpes infections with polysubstituted benzimidazoles

  摘要：

  一种治疗单纯疱疹病毒感染的方法，包括向受感染宿主投与以下化合物中的一种，或其在药学上可接受的盐或制剂，所述化合物具有以下公式： ##STR1## 其中：R.sub.1为H，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为H，R.sub.5为Br，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物52）；R.sub.1为H，R.sub.2为NO.sub.2，R.sub.3为NO.sub.2，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物61）；R.sub.1为Cl，R.sub.2为H，R.sub.3为Cl，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物81）；R.sub.1为H，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为H，R.sub.5为I，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物83a）；R.sub.1为Br，R.sub.2为Br，R.sub.3为H，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物85）；R.sub.1为H，R.sub.2为Br，R.sub.3为Cl，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物95）；R.sub.1为H，R.sub.2为Cl，R.sub.3为Br，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物99）；R.sub.1为H，R.sub.2为I，R.sub.3为I，R.sub.4为H，R.sub.5为Cl，R.sub.6为β-D-核糖呋喃（在文本中标记为化合物107）；R.sub.1为H，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为H，R.sub.5为Cl，R.sub.6为2'-脱氧-β-D-erythro-戊呋喃核苷（在文本中标记为化合物111）；R.sub.1为H，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为H，R.sub.5为Br，R.sub.6为2'-脱氧-β-D-erythro-戊呋喃核苷（在文本中标记为化合物112）；R.sub.1为Cl，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为Cl，R.sub.5为Cl，R.sub.6为（1,3-二羟基-2-丙氧基）甲基（在文本中标记为化合物155）；R.sub.1为Cl，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为Cl，R.sub.5为NH.sub.2，R.sub.6为（1,3-二羟基-2-丙氧基）甲基（在文本中标记为化合物156）；R.sub.1为Cl，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为Cl，R.sub.5为OCH.sub.3，R.sub.6为2-羟基乙氧基甲基（在文本中标记为化合物166a）；R.sub.1为Cl，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为Cl，R.sub.5为NH.sub.2，R.sub.6为2-羟基乙氧基甲基（在文本中标记为化合物167）；R.sub.1为H，R.sub.2为Cl，R.sub.3为Cl，R.sub.4为H，R.sub.5为NH.sub.2，R.sub.6为苄基（在文本中标记为化合物182）。

  公开号：

  US05712255A1
• 作为产物：
  描述：

  5,6-二氟-1H-苯并咪唑 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 copper dichloride 、 sodium nitrite 作用下， 反应 2.17h， 生成 2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Evaluation of 2-Chloro-5,6-dihalo-1-β-d-ribofuranosylbenzimidazoles as Potential Agents for Human Cytomegalovirus Infections

  摘要：

  2-Chloro-5,6-difluorobenzimidazole (8) was prepared from 4,5-difluoro-2-nitroaniline (5) via successive reduction, cyclization, and diazotization reactions. 2-Chloro-5,6-dibromobenzimidazole (10) was obtained by a direct bromination of 2-chlorobenzimidazole (9) with bromine-water. 2-Chloro-5,6-diiodobenzimidazole (15) was synthesized by a stepwise transformation of the nitro functions of 2-chloro-5,6-dinitrobenzimidazole (11) into iodo groups via diazotization reactions. Ribosylation of 8, 10, and 15 gave the respective beta nucleosides 16a-c as the major products along with a small amount of the alpha anomers 17a-c. Deprotection of 16a-c afforded the corresponding free beta nucleo sides 2-chloro-5,6-difluoro-1-beta-D-ribofuranosylbenzimidazole (2), 2-chloro-5,D-dibromo-1-beta-D-ribofuranosylbenzimidazole (3), and 2-chloro-5,6-diiodo-1-beta-D-ribofuranosylbenzimidazole (4). Similar deprotection of the alpha anomers (17a-c) resulted in a removal of the acetyl protecting groups and a concomitant cyclization to give the 2,2'-O-cyclonucleosides (18a-c). Most of the benzimidazole heterocycles, but not the difluoro analog, were active against human cytomegalovirus (HCMV) (IC50's = 3-40 mu M) and herpes simplex virus type 1 (HSV-1) (IC50's = 50-90 mu M). This activity, however, was not well separated from cytotoxicity, IC50's = 10-100 mu M. The corresponding unsubstituted, the 5,6-dimethyl, and the 5,6-difluoro ribonucleosides (19, 20, and 2, respectively), were inactive against both viruses. Similar to the previously reported 2,5,6-trichloro analog (TCRB), the 5,6-dibromo ribonucleoside 3 was active against HCMV (IC50 approximate to 4 mu M) but more cytotoxic than TCRB. The 5,6-diiodo analog 4 also was active (IC50 approximate to 2 mu M) but more cytotoxic (IC50 = 10-20 mu M) than either 3 or TCRB. The cyclonucleosides were inactive against both viruses and not cytotoxic, or slightly active with corresponding cytotoxicity. The order of activity against HCMV of the dihalobenzimidazole ribonucleosides was I similar or equal to Br similar or equal to Cl much greater than F > H = CH3. The order of cytotoxicity among the most active compounds, however, was I > Br > Cl, thereby establishing that TCRB had the best antiviral properties.

  DOI：

  10.1021/jm960462g

文献信息

• Polysubstituted benzimidazoles as antiviral agents
  申请人：The Regents of the University of Michigan

  公开号：US05360795A1

  公开（公告）日：1994-11-01

  This invention relates to novel polysubstituted benzimidazoles and compositions and their use in the treatment of viral infections. The polysubstituted benzimidazoles and compositions of the present invention exhibit antiviral properties against viruses of the herpes family, particularly human cytomegalovirus (HCMV) and herpes simplex viruses (HSV). Preferred polysubstituted benzimidazoles of the invention are 2,5,6-Trichloro-1-(.beta.-D-5-deoxyribofuranosyl)benzimidazole and 2-bromo-5,6-dichloro-1-(5-deoxy-.beta.-D-ribofuranosyl)benzimidazole.

  这项发明涉及新型多取代苯并咪唑及其组合物，以及它们在治疗病毒感染中的用途。本发明的多取代苯并咪唑和组合物对疱疹病毒家族的病毒，特别是人类巨细胞病毒（HCMV）和单纯疱疹病毒（HSV）表现出抗病毒特性。该发明的首选多取代苯并咪唑是2,5,6-三氯-1-(β-D-5-脱氧核糖呋喃糖基)苯并咪唑和2-溴-5,6-二氯-1-(5-脱氧-β-D-核糖呋喃糖基)苯并咪唑。
• POLYSUBSTITUTED BENZIMIDAZOLES AS ANTIVIRAL AGENTS
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：EP0556334A1

  公开（公告）日：1993-08-25
• EP0556334A4
  申请人：——

  公开号：EP0556334A4

  公开（公告）日：1995-03-29
• US5360795A
  申请人：——

  公开号：US5360795A

  公开（公告）日：1994-11-01
• US5574058A
  申请人：——

  公开号：US5574058A

  公开（公告）日：1996-11-12