2-Chloro-5,6-dibromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole | 142356-80-7

• 分子结构分类: 有机化合物
• 英文名称: 2-Chloro-5,6-dibromo-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)benzimidazole
• 英文别名: 2-Chloro-5,6-dibromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazole；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(5,6-dibromo-2-chlorobenzimidazol-1-yl)oxolan-2-yl]methyl acetate
• CAS: 142356-80-7
• 化学式: C₁₈H₁₇Br₂ClN₂O₇
• 分子量: 568.603
• InChiKey: LTGCQNBYXQYNOF-QBPKDAKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：
  8

反应信息

• 作为反应物：
  描述：

  2-Chloro-5,6-dibromo-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 5.0h， 以to give 337 mg (2 crops, 76%) of 57的产率得到2-chloro-5,6-dibromo-1-(β-D-ribofuranosyl)benzimidazole
  参考文献：
  名称：

  Polysubstituted benzimidazoles as antiviral agents

  摘要：

  本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方面的应用。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，尤其是人类巨细胞病毒（HCMV）和单纯疱疹病毒（HSV）表现出抗病毒特性。

  公开号：

  US05646125A1
• 作为产物：
  描述：

  2-氯苯并咪唑 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 水 、 溴 作用下， 反应 23.75h， 生成 2-Chloro-5,6-dibromo-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

• Treatment of herpes infections with polysubstituted benzimidazoles
  申请人：The Regents of the University of Michigan

  公开号：US05712255A1

  公开（公告）日：1998-01-27

  A method for treating a herpes viral infection comprising administering to the infected host a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt or formulation thereof, selected from the group consisting of compounds having the following formula: ##STR1## wherein: R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Br and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 52 in the text); R.sub.1 is H, R.sub.2 is NO.sub.2, R.sub.3 is NO.sub.2, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 61 in the text); R.sub.1 is Cl, R.sub.2 is H, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 81 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is I and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 83a in the text); R.sub.1 is Br, R.sub.2 is Br, R.sub.3 is H, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 85 in the text); R.sub.1 is H, R.sub.2 is Br, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 95 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Br, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 99 in the text); R.sub.1 is H, R.sub.2 is I, R.sub.3 is I, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is .beta.-D-ribofuranosyl (denoted compound 107 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Cl and R.sub.6 is 2'-deoxy-.beta.-D-erythro-pentofuranosyl (denoted compound 111 in the text); R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is Br and R.sub.6 is 2'-deoxy-.beta.-D-erythro-pentofuranosyl (denoted compound 112 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is Cl and R.sub.6 is (1,3-dihydroxy-2-propoxy)methyl (denoted compound 155 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is NH.sub.2 and R.sub.6 is (1,3-dihydroxy-2-propoxy)methyl (denoted compound 156 in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is OCH.sub.3 and R.sub.6 is 2-hydroxyethoxymethyl (denoted compound 166a in the text); R.sub.1 is Cl, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is Cl, R.sub.5 is NH.sub.2 and R.sub.6 is 2-hydroxyethoxymethyl (denoted compound 167 in the text); and R.sub.1 is H, R.sub.2 is Cl, R.sub.3 is Cl, R.sub.4 is H, R.sub.5 is NH.sub.2 and R.sub.6 is benzyl (denoted compound 182 in the text).

  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）。
• 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