2-溴-5,6-二氯-1H-苯并咪唑 | 142356-40-9

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-溴-5,6-二氯-1H-苯并咪唑
• 英文名称: 2-bromo-5,6-dichloro-1H-1,3-benzodiazole
• 英文别名: 2-Bromo-5,6-dichloro-1H-benzimidazole；2-bromo-5,6-dichloro-1H-benzo[d]imidazole；2-bromo-5,6-dichlorobenzimidazole；2-Bromo-5,6dichlorobenzimidazole
• CAS: 142356-40-9
• 化学式: C₇H₃BrCl₂N₂
• 分子量: 265.924
• InChiKey: KEZMBKQTCPNSOF-UHFFFAOYSA-N

物化性质

• 熔点：
  233-234 °C
• 沸点：
  414.8±48.0 °C(Predicted)
• 密度：
  1.967±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  2-溴-5,6-二氯-1H-苯并咪唑 在 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 乙腈 为溶剂， 反应 17.17h， 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
• 作为产物：
  描述：

  4,5-二氯-2-硝基苯胺 在 亚硝酸特丁酯 、 氢气 、 镍 、 copper(ll) bromide 作用下， 以 甲醇 、 乙醇 、 水 、 丙酮 为溶剂， 反应 2.0h， 生成 2-溴-5,6-二氯-1H-苯并咪唑
  参考文献：
  名称：

  Design, Synthesis, and Antiviral Evaluations of 1-(Substituted benzyl)-2-substituted-5,6-dichlorobenzimidazoles as Nonnucleoside Analogues of 2,5,6-Trichloro-1-(β-d-ribofuranosyl)benzimidazole

  摘要：

  We have recently reported that certain ribosylated polyhalogenated benzimidazoles are potent and selective inhibitors of HCMV replication at noncytotoxic concentrations. To extend the structure-activity relationship beyond these first-generation compounds, we alkylated 5,6-dichloro-2-substituted-benzimidazoles with either a series of substituted benzyl halides or (2-bromoethyl)benzene to obtain five series of nonnucleoside analogues. Evaluation of these compounds for activity against herpes viruses revealed that the new compounds were less active than the benzimidazole ribonucleosides against human cytomegalovirus (HCMV) and inactive against herpes simplex virus type 1 (HSV-1). However, as part of our broader antiviral testing, we found that some of these compounds were active against HIV. Comparisons of the biological data revealed that a chloro or bromo group was required at the 2-position for the best separation of activity against HIV and cytotoxicity. Evaluation of the most active compounds against drug-resistant HIV suggested that they act by a mechanism other than inhibition of reverse transcriptase.

  DOI：

  10.1021/jm970559i

文献信息

• Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA
  作者：Meral Tunçbilek、Tuluğ Kiper、Nurten Altanlar

  DOI：10.1016/j.ejmech.2008.06.026

  日期：2009.3

  The novel benzimidazole derivatives (3, 5, 8, 9, 12–14, 18–41) were prepared in this paper and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolates), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. Compounds 24–26 which have no substitution of N-1 position displayed better antibacterial

  新颖的苯并咪唑衍生物（3，5，8，9，12 - 14，18 - 41）在本文中和对这些化合物的抗微生物活性来制备金黄色葡萄球菌，耐甲氧西林金黄色葡萄球菌（MRSA，标准和临床分离物），枯草芽孢杆菌，大肠杆菌和白色念珠菌进行了评估。化合物24 – 26那些没有取代N-1位的药物对两种耐药细菌（MRSA，标准品和临床分离株）均显示出比标准品（环丙沙星，氨苄青霉素和苏木素）更好的抗菌活性。这些衍生物（24 - 26），2,5,6- trihalogenobenzimidazole类似物（8，12），5,6-二氯-2-氨基衍生物（13），和5-氯-2-（4-苄氧基苯基）苯并咪唑（35）表现出最强的抗菌活性，MIC 3.12μg/ ml对金黄色葡萄球菌。
• [EN] METHOD OF PREPARATION OF NOVEL NUCLEOSIDE ANALOGS AND USES<br/>[FR] PROCEDE POUR PREPARER DE NOUVEAUX ANALOGUES DE NUCLEOSIDE, ET LEURS UTILISATIONS
  申请人：AUSPEX PHARMACEUTICALS INC

  公开号：WO2005049582A1

  公开（公告）日：2005-06-02

  Processes for the preparation of racemic and optically active nucleoside analogs of formula (A) are described. These compounds are useful as anti-infective agents, antisense therapeutic agents and hybridization assay probes.

  描述了制备式(A)的外消旋和光学活性核苷类似物的过程。这些化合物可用作抗感染剂、反义治疗剂和杂交分析探针。
• 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。
• Design, Synthesis, and Antiviral Evaluation of 2-Deoxy-D-Ribosides of Substituted Benzimidazoles as Potential Agents for Human Cytomegalovirus Infections
  作者：Ruiming Zou、Etsuko Kawashima、George A. Freeman、George W. Koszalka、John C. Drach、Leroy B. Townsend

  DOI：10.1080/15257770008033000

  日期：2000.1

  Stereoselective glycosylation of 2,5,6-trichlorobenzimidazole (1b), 2-bromo-5,6-dichlorobenzimidazole (1c), 5,6-dichlorobenzimidazole (1d), 5,6-dichlorobenzimidazole-2-thione (1e), 5,6-dichloro-2-(methylthio)benzimidazole (1f), 2-(benzylthio)-5,6-dichlorobenzimidazole (1g), and 2-chloro-5,6-dimethylbenzimidazole (1h) with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranosyl chloride was achieved to give the

  2,5,6-三氯苯并咪唑（1b），2-溴-5,6-二氯苯并咪唑（1c），5,6-二氯苯并咪唑（1d），5,6-二氯苯并咪唑-2-硫酮（1e），5的立体选择性糖基化带有2-deoxy-3的1,6-二氯-2-（甲硫基）苯并咪唑（1f），2-（苄硫基）-5,6-二氯苯并咪唑（1g）和2-氯-5,6-二甲基苯并咪唑（1h），获得了5-二-对-甲苯甲酰基-α-D-赤型五呋喃糖酰氯，得到所需的β-核苷2b-h。随后的脱保护得到相应的游离β-D-2-脱氧核糖苷3b-h。通过用甲醇甲醇钠处理2b来合成2-甲氧基衍生物3i。用叠氮化锂置换2b的2-氯基，然后去除保护基，得到2-叠氮基-5，6-二氯苯并咪唑衍生物（5）。通过在阮内镍上氢解5获得2-氨基衍生物（6）。使用2'-脱氧尿苷（7），N-脱氧核糖呋喃糖基转移酶和1d制备5,6-二氯-2-异丙基氨基-1-（2-脱氧-β-D-赤-呋喃呋喃糖基）苯并咪唑（1
• Synthesis and Evaluation of a Series of 2′-Deoxy Analogues of The Antiviral Agent 5,6-Dichloro-2-Isopropylamino-1-(β-L-Ribofuranosyl)-1H-Benzimidazole (1263W94)
  作者：Joseph H. Chan、Stanley D. Chamberlain、Karen K. Biron、Michelle G. Davis、Robert J. Harvey、Dean W. Selleseth、Ronna E. Dornsife、Ernest H. Dark、Lloyd W. Frick、Leroy B. Townsend、John C. Drach、George W. Koszalka

  DOI：10.1080/15257770008032999

  日期：2000.1

  and branched alkylamino groups were needed for potent activity against HCMV. Three analogues 3a, 3b and 3d were as potent as 1263W94. Further evaluation of two analogues, 3a and 3b, suggested that these 2'-deoxy analogues may act via a novel mechanism of action similar to that of 1263W94. These 2'-deoxy analogues generally lacked cytotoxicity in vitro. Pharmacokinetic parameters in mice and protein

  合成了抗病毒剂5,6-二氯-2-异丙基氨基-1-（β-L-核呋喃糖基）-1H-苯并咪唑（1263W94）的一系列2'-脱氧类似物，并评估了其对人巨细胞病毒（HCMV）的活性并具有细胞毒性。苯并咪唑部分中的2-取代基对应于1263W94系列中使用的那些。通常，如在1263W94系列中发现的那样，环状和支链烷基氨基基团需要有效的抗HCMV活性。三个类似物3a，3b和3d与1263W94一样有效。对两个类似物3a和3b的进一步评估表明，这些2'-脱氧类似物可以通过类似于1263W94的新颖作用机制起作用。这些2'-脱氧类似物通常在体外缺乏细胞毒性。小鼠的药代动力学参数和3a的蛋白质结合特性与1263W94非常相似。但是，3a的口服生物利用度仅为1263W94观察到的一半。