2,2'-[1,5-pentanediylbis(oxy-1,4-phenylene)]bis-1H-benzimidazole | 1031382-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2,2'-[1,5-pentanediylbis(oxy-1,4-phenylene)]bis-1H-benzimidazole
• 英文别名: 2,2'-[1,5-pentanediylbis(4-oxyphenylene)]bis-(1H-benzimidazole)；1,5-bis[4-(1H-benzimidazol-2-yl)phenoxy]pentane；1,5-Bis[4-(2-benzimidazolyl)phenoxy]pentane；2-[4-[5-[4-(1H-benzimidazol-2-yl)phenoxy]pentoxy]phenyl]-1H-benzimidazole
• CAS: 1031382-64-5
• 化学式: C₃₁H₂₈N₄O₂
• 分子量: 488.589
• InChiKey: FVYHAXWUPTYOAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  对羟基苯甲醛 在 sodium disulfite 、 potassium carbonate 作用下， 以 乙醇 、 水 为溶剂， 反应 8.25h， 生成 2,2'-[1,5-pentanediylbis(oxy-1,4-phenylene)]bis-1H-benzimidazole
  参考文献：
  名称：

  Fragment-Based Design of Symmetrical Bis-benzimidazoles as Selective Inhibitors of the Trimethoprim-Resistant, Type II R67 Dihydrofolate Reductase

  摘要：

  The continuously increasing use of trimethoprim as a common antibiotic for medical use and for prophylactic application in terrestrial and aquatic animal farming has increased its prevalence in the environment. This has been accompanied by increased drug resistance, generally in the form of alterations in the drug target, dihydrofolate reductase (DHFR). The most highly resistant variants of DHFR are known as type II DHFR, among which R67 DHFR is the most broadly studied variant. We report the first attempt at designing specific inhibitors to this emerging drug target by fragment-based design. The detection of inhibition in R67 DHFR was accompanied by parallel monitoring of the human DHFR, as an assessment of compound selectivity. By those means, small aromatic molecules of 150-250 g/mol (fragments) inhibiting R67 DHFR selectively in the low millimolar range were identified. More complex, symmetrical bis-benzimidazoles and a bis-carboxyphenyl were then assayed as fragment-based leads, which procured selective inhibition of the target in the low micromolar range (K-i = 2-4 mu M). The putative mode of inhibition is discussed according to molecular modeling supported by in vitro tests.

  DOI：

  10.1021/jm201645r

文献信息

• Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids
  作者：Héctor Torres-Gómez、Emanuel Hernández-Núñez、Ismael León-Rivera、Jorge Guerrero-Alvarez、Roberto Cedillo-Rivera、Rosa Moo-Puc、Rocío Argotte-Ramos、María del Carmen Rodríguez-Gutiérrez、Manuel Jesús Chan-Bacab、Gabriel Navarrete-Vázquez

  DOI：10.1016/j.bmcl.2008.05.009

  日期：2008.6

  A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)<1 microM)

  使用短合成路线制备了十种来自苯并咪唑和喷他idine的新型杂种。与喷他idine和甲硝唑相比，每种化合物均在体外针对阴道毛滴虫，兰氏贾第鞭毛虫，溶血性变形杆菌，墨西哥利什曼原虫和伯氏疟原虫进行了测试。一些类似物对前四个原生动物在低微摩尔范围（IC（50）<1 microM）中显示出高生物活性，这使它们比任何一个标准都具有更强的效力。1,5-双[4-（5-甲氧基-1H-苯并咪唑-2-基）苯氧基]戊烷（2）对G的效力分别高3到9倍。兰比兰甲硝唑和戊tam分别。该化合物分别比喷他idine具有23.，108-和13-倍的活性，其对阴道隐孢子虫，溶组织性大肠杆菌和墨西哥乳杆菌具有更高的活性。
• Visible-Light-Promoted Synthesis of Benzimidazoles
  作者：Sehyun Park、Jaehun Jung、Eun Jin Cho

  DOI：10.1002/ejoc.201402141

  日期：2014.7

  A simple and environmentally-friendly synthetic method for benzimidazoles, which are important structural motifs in many applications owing to their various biological functions, has been developed. The reaction of o-phenylenediamine and a variety of aliphatic/aromatic aldehydes in methanol proceeds at room temperature with only natural sources, molecular oxygen and visible light.

  苯并咪唑由于具有多种生物学功能而在许多应用中是重要的结构基序，因此已经开发出一种简单且环境友好的苯并咪唑合成方法。邻苯二胺和各种脂肪族/芳香族醛在甲醇中的反应在室温下仅在天然来源、分子氧和可见光下进行。
• Novel bisbenzimidazoles with antileishmanial effectiveness
  作者：Annie Mayence、Aurélie Pietka、Margaret S. Collins、Melanie T. Cushion、Babu L. Tekwani、Tien L. Huang、Jean Jacques Vanden Eynde

  DOI：10.1016/j.bmcl.2008.03.020

  日期：2008.4

  A small library of 2,2'-[(alpha,omega-alkanediylbis(oxyphenylene)]bis-1H-benzimidazoles has been prepared and screened in vitro against Pneumocystis carinii, Trypanosoma brucei rhodesiense, and Leishmania donovani. Among the six tested compounds two derivatives emerged as promising hits characterized by IC50 values lower than that determined for pentamidine against L. donovani. (C) 2008 Elsevier Ltd. All rights reserved.
• Bis(oxyphenylene)benzimidazoles: A novel class of anti-Plasmodium falciparum agents
  作者：Annie Mayence、Jean Jacques Vanden Eynde、Marcel Kaiser、Reto Brun、Nigel Yarlett、Tien L. Huang

  DOI：10.1016/j.bmc.2011.10.039

  日期：2011.12

  A small library of 26 2,2'-[alkane-alpha,omega-diylbis(oxyphenylene)] bis-1H-benzimidazoles has been prepared and evaluated against Giardia intestinalis, Entamoeba histolytica, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani, and Plasmodium falciparum. Among the tested compounds, eight derivatives (17, 19, 20, 24, 27, 30, 32 and 35) exhibited an anti-Plasmodium falciparum activity characterized by IC50 values in the range of 180-410 nM (0.11-0.21 mu g/mL) and selectivity indexes (IC50 rat skeletal myoblasts L6 cells vs IC50 P. falciparum K1 strain) varying between 92 and more than 450. Two of the eight novel drug leads, namely compounds 19 and 32, were also active against G. intestinalis and L. donovani with selectivity indexes of 122 and > 164 respectively. (C) 2011 Elsevier Ltd. All rights reserved.
• BISBENZIMIDAZOLES AS ANTIMALARIAL AGENTS
  申请人：Université de Mons-Hainaut

  公开号：EP2194981A1

  公开（公告）日：2010-06-16