2-bromo-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole | 142356-43-2

• 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-bromo-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole
• 英文别名: benzimidazole 2-bromo-5, 6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole；2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl) benzimidazole；2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole；bromudichlororibobenzimidazole；BDCRB；5,6-dichloro-2-bromo-1-(β-D-ribofuranosyl)benzimidazole；(2R,3R,4S,5R)-2-(2-bromo-5,6-dichlorobenzimidazol-1-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 142356-43-2
• 化学式: C₁₂H₁₁BrCl₂N₂O₄
• 分子量: 398.04
• InChiKey: NMAMPJIAXSGTLN-GWOFURMSSA-N

物化性质

• 沸点：
  650.2±65.0 °C(Predicted)
• 密度：
  2.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.7
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-bromo-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 2-bromo-5,6-dichloro-5'-O-L-aspartyl-1-β-D-ribofuranosylbenzimidazole
  参考文献：
  名称：

  Amino Acid Ester Prodrugs of the Antiviral Agent 2-Bromo-5,6-dichloro-1-(β-d-ribofuranosyl)benzimidazole as Potential Substrates of hPEPT1 Transporter

  摘要：

  Amino acid ester prodrugs of 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) were synthesized and evaluated for their affinity for hPEPT1, an intestinal oligopeptide transporter. Assays of competitive inhibition of [H-3]glycylsarcosine (Gly-Sar) uptake in HeLa/hPEPT1 cells by the amino acid ester prodrugs of BDCRB suggested their 2- to 4-fold higher affinity for hPEPT1 compared to BDCRB. Further, promoieties with hydrophobic side chains and L-configuration were preferred by the hPEPT1 transporter.

  DOI：

  10.1021/jm049450i
• 作为产物：
  描述：

  4,5-二氯邻苯二胺 在 三氟甲磺酸三甲基硅酯 、 氨 、 氢溴酸 、 copper(I) bromide 、 sodium nitrite 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 19.17h， 生成 2-bromo-5,6-dichloro-1-β-D-ribofuranosylbenzimidazole
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Activity of Certain 2,5,6-Trihalo-1-(.beta.-D-ribofuranosyl)benzimidazoles

  摘要：

  A new series of 2-substituted 5,6-dichlorobenzimidazole ribonucleosides has been synthesized and tested for activity against two human herpes viruses and for cytotoxicity. 2,5,6-Trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) was prepared by ribosylation of the heterocycle 2,5,6-trichlorobenzimidazole followed by a removal of the protecting groups. The 2-bromo derivative (BDCRB) was made in a similar fashion from 2-bromo-5,6-dichlorobenzimidazole. In contrast, the 2-iodo derivative presented a more difficult problem since the appropriate heterocycle was unavailable. This prompted us to prepare the 2-amino derivative followed by nonaqueous diazotization and removal of the blocking groups. Biological evaluation revealed marked differences in the activities of these compounds and the closely related known compound 5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DRB). DRB was weakly active against both human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1), (IC50's = 42 and 30 mu M, respectively) but-was cytotoxic to uninfected human foreskin fibroblasts and KB cells in the same dose range. Similar results were obtained with the heterocycle 2,5,6-trichlorobenzimidazole. In marked contrast, the ribonucleoside of 2,5,6-trichlorobenzimidazole (TCRB) was active against HCMV (IC50 = 2.9 mu M, plaque assay; IC50 = 1.4 mu M, yield assay) but only weakly active against HSV-1 (IC50 = 102 mu M, plaque assay). Little to no cytotoxicity was observed in HFF and KB cells at concentrations up to 100 mu M. By changing the substituent at the 2-position from chlorine to bromine (BDCRB), a 4-fold increase in activity against HCMV was observed without any significant increase in cytotoxicity. In contrast, the 2-I and 2-NH2 derivatives were only weakly active against HCMV and HSV-1 with activity not well-separated from cytotoxicity. These data establish that for maximum activity against HCMV with separation from cytotoxicity, ribose is preferred at the 1-position and that Cl or Br is apparently preferred at the 2-position. The activity and selectivity of both TCRB and BDCRB were better than that observed with either ganciclovir or foscarnet.

  DOI：

  10.1021/jm00020a025

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。
• Process for preparing substituted benzimidazole compounds
  申请人：——

  公开号：US20030191127A1

  公开（公告）日：2003-10-09

  The invention relates to new methods of preparing substituted benzimidazole compounds, such as 2-bromo-5,6-dichlorobenzimidazole, which are useful in the preparation of compounds having antiviral activity.

  这项发明涉及一种制备取代苯并咪唑化合物的新方法，例如2-溴-5,6-二氯苯并咪唑，这些化合物在具有抗病毒活性的化合物的制备中非常有用。
• Polysubstituted benzimidazole nucleosides as antiviral agents
  申请人：The Regents of the University of Michigan

  公开号：US05248672A1

  公开（公告）日：1993-09-28

  This invention relates to novel polysubstituted benzimidazole nucleosides and compositions and their use in the treatment of viral infections, particulary those caused by human cytomegalovirus and herpes simplex virus. Such substituted compounds exhibit antiviral properties superior to their parent compounds and low leve SPONSORSHIP This invention was made with government support under Contract No. NO1 Al 42554 and NO1 Al 72641 awarded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The government has certain rights in this invention.

  本发明涉及新型多取代苯并咪唑核苷及其组合物，以及它们在治疗病毒感染中的应用，特别是人类巨细胞病毒和单纯疱疹病毒引起的感染。这些取代化合物表现出比它们的原始化合物更优异的抗病毒性能和低水平的赞助。本发明是在国家卫生研究院过敏与传染病国家研究所授予的合同号NO1 Al 42554和NO1 Al 72641的政府支持下完成的。政府对本发明享有某些权利。
• Benzimidazoles and Methods of Using Same
  申请人：University of Utah Research Foundation

  公开号：US20210079008A1

  公开（公告）日：2021-03-18

  The present disclosure is concerned with benzimidazole compounds and methods of using these compounds for the treatment of hepatitis (e.g., hepatitis C), RNA virus infections (e.g., Zika virus, dengue virus, Powassan virus, Chikungunya virus, Enterovirus, respiratory syntactical virus (RSV), Rift Valley fever, Influenza virus, Tacaribe virus, Mayaro virus, West Nile virus, yellow fever virus, and coronavirus), and disorders of uncontrolled cellular proliferation (e.g., cancer). This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本公开涉及苯并咪唑化合物及其使用方法，用于治疗肝炎（例如丙型肝炎）、RNA病毒感染（例如寨卡病毒、登革热病毒、波瓦桑病毒、基孔肯雅病毒、肠道病毒、呼吸道合胞病毒（RSV）、裂谷热、流感病毒、塔卡里贝病毒、马亚罗病毒、西尼罗河病毒、黄热病毒和冠状病毒）以及细胞增殖失控性疾病（例如癌症）。本摘要旨在作为特定技术领域搜索的扫描工具，不限于本发明。
• METHOD OF TREATING VIRAL INFECTIONS
  申请人：EPIPHANY BIOSCIENCES

  公开号：US20150050241A1

  公开（公告）日：2015-02-19

  The present invention is directed to methods and compositions employing 9-(4-hydroxy-2-(hydroxymethyl)butyl)guanine (“H2G”) or derivatives or analogs thereof for the treatment of viral diseases, as well as for the treatment of other conditions, including, but not limited to, cancer, chronic fatigue syndrome, Alzheimer's disease, multiple sclerosis and Graves' disease. The H2G or derivative or analog thereof can be administered in a pharmaceutical composition and can be administered with an additional antiviral therapeutic agent or another agent for the treatment of other conditions.

  本发明涉及使用9-（4-羟基-2-（羟甲基）丁基）鸟嘌呤（“H2G”）或其衍生物或类似物的方法和组合物，用于治疗病毒性疾病，以及用于治疗其他疾病，包括但不限于癌症、慢性疲劳综合征、阿尔茨海默病、多发性硬化症和格雷夫斯病。 H2G或其衍生物或类似物可以在药物组合物中给予，并且可以与其他抗病毒治疗药物或其他治疗其他疾病的药物一起给予。