2,5,6-trichloro-1-β-D-ribofuranosyl-1H-benzimidazole | 62908-78-5

• 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: 2,5,6-trichloro-1-β-D-ribofuranosyl-1H-benzimidazole
• 英文别名: 2,5,6-trichloro-1-(β-D-ribofuranosyl)benzimidazole；2,5,6-trichloro-1-β-D-ribofuranosylbenzimidazole；1-(β-D-ribofuranosyl)-2,5,6-trichloro-1H-benzimidazole；(2R,3S,4R,5R)-2-(hydroxymethyl)-5-(2,5,6-trichlorobenzimidazol-1-yl)oxolane-3,4-diol
• CAS: 62908-78-5
• 化学式: C₁₂H₁₁Cl₃N₂O₄
• 分子量: 353.589
• InChiKey: BSDCIRGNJKZPFV-GWOFURMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 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：

  2,5,6-trichloro-1-β-D-ribofuranosyl-1H-benzimidazole 在 吡啶 、 4-二甲氨基吡啶 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 98.75h， 生成 2,5,6-trichloro-1-(3-deoxy-3-fluoro-β-D-xylofuranosyl)benzimidazole
  参考文献：
  名称：

  Synthesis of Fluorosugar Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole as Antivirals with Potentially Increased Glycosidic Bond Stability

  摘要：

  The metabolic instability in vivo of the glycosidic bond of 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) prompted us to design and synthesize the hitherto unreported fluorinated benzimidazole nucleosides 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole, 2,5,6-trichloro-1-(3-deoxy-3-fluoro-beta-D-ribofuranosyl)benzimidazole, and 2-bromo-5,6-dichloro-1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)benzimidazole. TCRB was converted into the 2',5'-ditrityl and 3'5'-dinitryl derivatives, which were fluorinated with DAST and deprotected to yield 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) and 2,5,6-trichloro-1(3-deoxy-3-fluoro-beta-D-xylofuranosyl)benzimidazole. The resulting low over yield (5%) of 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole encouraged us to develop an alternative route. The heterocycle 2,5,6-trichlorobenzimidazole was condensed with 1-bromo-3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose to give, after deprotection, 2,5,6-trichloro-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)benzimidazole in a 50% overall yield. The 2'-deoxy-2'-fluoro-beta-D-ribofuranosyl compounds were prepared using 2'-deoxy-2'-fluorouridine, N-deoxyribofuranosyl transferase, and 5,6-dichlorobenzimidazole. Functionalization of the C2 position then gave the desired derivatives. Antiviral and cytotoxicity testing revealed that the deoxy fluoro arabinofuranosyl, xylofuranosyl, and ribofuranosyl derivatives were less active against human cytomegalovirus and more cytotoxic than TCRB.

  DOI：

  10.1021/jm990219s
• 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 、 copper dichloride 、 sodium nitrite 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 19.33h， 生成 2,5,6-trichloro-1-β-D-ribofuranosyl-1H-benzimidazole
  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

• Indole antiviral compositions and methods
  申请人：Townsend B. Leroy

  公开号：US20050143329A1

  公开（公告）日：2005-06-30

  The present invention provides novel chemical compounds, and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

  本发明提供了新的化合物和其使用方法。特别地，本发明提供吲哚衍生物（例如如式（I）所示）和相关化合物以及使用吲哚衍生物和相关化合物作为治疗剂治疗多种疾病的方法，包括与病毒感染和心血管疾病有关的疾病。
• 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和其组合物，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母体化合物更优越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和传染病研究所授予的合同号码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。
• Polysubstituted benzimidazoles as antiviral agents
  申请人：The Regents of the University of Michigan

  公开号：US05705490A1

  公开（公告）日：1998-01-06

  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).

  本发明涉及新型多取代苯并咪唑化合物及其组合物，并且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化合物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。
• Benzimidazole derivatives and medical uses thereof
  申请人：Kikuchi Norhiko

  公开号：US20080038242A1

  公开（公告）日：2008-02-14

  The present invention provides benzimidazole derivatives represented by the following formula (I) or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exert an inhibitory activity on sodium-dependent nucleoside transporter 2 and are useful for a disease associated with an abnormality of plasma uric acid level. The compounds of the present invention are useful for the prevention or treatment of gout, hyperuricemia, urinary lithiasis, hyperuricemic nephropathy or the like. In the formula, n is 1 or 2; R 1 and R 2 are H, a halogen atom, cyano group, optionally substituted alkyl group, optionally substituted aryl group or the like; R 3 is H, a halogen atom, optionally substituted alkyl group or the like; R 4 and R 5 are H, a halogen atom, OH or the like; and R 6 and R X are H or OH: R Y is F or OH.

  本发明提供以下式(I)所表示的苯并咪唑衍生物或其药学上可接受的盐或前药，其对钠依赖性核苷酸转运体2具有抑制活性，并可用于与血浆尿酸水平异常相关的疾病。本发明的化合物可用于痛风、高尿酸血症、尿路结石、高尿酸性肾病等的预防或治疗。在式中，n为1或2；R1和R2为H、卤素原子、氰基、可选取代烷基、可选取代芳基或类似物；R3为H、卤素原子、可选取代烷基或类似物；R4和R5为H、卤素原子、OH或类似物；R6和RX为H或OH；RY为F或OH。
• Indole Antiviral Compositions And Methods
  申请人：Townsend Leroy B.

  公开号：US20090281052A1

  公开（公告）日：2009-11-12

  The present invention provides novel chemical compounds, and methods for their use. In particular, the present invention provides indole derivatives (e.g. as shown in Formula (I)) and related compounds and methods of using indole derivatives and related compounds as therapeutic agents to treat a number of conditions, including those associated with viral infection and cardiovascular diseases.

  本发明提供了新型化合物及其使用方法。具体来说，本发明提供吲哚衍生物（例如如式（I）所示）和相关化合物，以及使用吲哚衍生物和相关化合物作为治疗剂治疗多种疾病的方法，包括与病毒感染和心血管疾病相关的疾病。