1-(4-氟苄基)-2-(1-哌嗪基)-1H-苯并咪唑 | 142617-98-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(4-氟苄基)-2-(1-哌嗪基)-1H-苯并咪唑
• 中文别名: 1-(4-氟苄基)-2-哌嗪-1H-苯并咪唑
• 英文名称: 1-(4-fluorobenzyl)-2-(piperazin-1-yl)-1H-benzo[d]imidazole
• 英文别名: 1-(4-fluorophenylmethyl)-2-(1-piperazinyl)-1H-benzimidazole；1-(4-Fluoro-benzyl)-2-piperazin-1-yl-1H-benzoimidazole；1-[(4-fluorophenyl)methyl]-2-piperazin-1-ylbenzimidazole
• CAS: 142617-98-9
• 化学式: C₁₈H₁₉FN₄
• 分子量: 310.374
• InChiKey: UBXGZTRRRHVEAJ-UHFFFAOYSA-N

物化性质

• 沸点：
  506.2±60.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  4-甲氧基苯乙醛 、 1-(4-氟苄基)-2-(1-哌嗪基)-1H-苯并咪唑 在 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium cyanoborohydride 作用下， 以 乙醇 为溶剂， 反应 19.0h， 生成 1-(4-fluorobenzyl)-2-(4-(4-methoxyphenethyl)-piperazin-1-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Astemizole analogues with reduced hERG inhibition as potent antimalarial compounds

  摘要：

  Astemizole is a H-1-antagonist endowed with antimalarial activity, but has hERG liabilities. Systematic structural modifications of astemizole led to the discovery of analogues that display very potent activity as inhibitors of the growth of the Plasmodium parasite, but show a decreased hERG inhibition, when compared to astemizole. These compounds can be used as starting point for the development of a new class of antimalarials. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.10.004
• 作为产物：
  描述：

  2-氯苯并咪唑 在 potassium carbonate 、 三乙胺 作用下， 以 丙酮 、 叔丁醇 为溶剂， 反应 48.0h， 生成 1-(4-氟苄基)-2-(1-哌嗪基)-1H-苯并咪唑
  参考文献：
  名称：

  阿司咪唑类似物的多级抗疟原虫活性和抑制血腥素形成为其作用方式的贡献者。

  摘要：

  利用药物重新定位方法衍生化阿司咪唑（AST），这是一种抗组胺药，其抗疟活性先前已在高通量筛选中确定。通过评估寄生虫的无性血液，肝脏和性配子分裂阶段，检查了其后类似物对疟原虫的生命周期的多阶段活性潜能。另外，对先前报道的血红素解毒对化合物作用方式的贡献进行了研究。17种衍生物中的10种对氯喹（CQ）敏感的恶性疟原虫NF54（PfNF54）菌株显示半数最大抑制浓度（IC50s）<0.1μM，同时对多药耐药菌株PfK1保持亚微摩尔效价，多数显示低与CQ交叉耐药的可能性。测试了选定的类似物（PfNF54-IC50 <0.1μM）对中国仓鼠卵巢（CHO）细胞的细胞毒性，发现其具有高度选择性（选择性指数> 100）。AST及其类似物针对配子体细胞的筛选显示了其对晚期恶性疟原虫配体细胞的中等活性（IC50：1-5μM），而对伯氏疟原虫肝阶段活性的评估则鉴定出一种化合物（3）的活性提高了3倍活性要比母体A

  DOI：

  10.1021/acsinfecdis.8b00272

文献信息

• [EN] BENZIMIDAZOLES FOR THE TREATMENT OF CANCER<br/>[FR] BENZIMIDAZOLES POUR LE TRAITEMENT D'UN CANCER
  申请人：MAX PLANCK GESELLSCHAFT

  公开号：WO2014027053A1

  公开（公告）日：2014-02-20

  The present invention relates to novel substituted benzimidazoles and stereoisomeric forms, prodrugs, solvates, hydrates and/or pharmaceutically acceptable salts of these compounds as well as pharmaceutical compositions containing at least one of these substituted benzimidazoles together with pharmaceutically acceptable carrier, excipient and/or diluents. Said novel substituted benzimidazoles binding to the prenyl binding pocket of PDEδ have been identified as useful for the prophylaxis and treatment of cancer by the inhibition of the binding of PDEδ to K-Ras and of oncogenic Ras signalling in cells by altering its localization leading to cell death or inhibition of proliferation.

  本发明涉及新型取代苯并咪唑和立体异构体形式，以及这些化合物的前药、溶剂化合物、水合物和/或药学上可接受的盐，以及含有至少一种这些取代苯并咪唑的药物组合物，与药学上可接受的载体、赋形剂和/或稀释剂一起。已经确定这些新型取代苯并咪唑结合到PDEδ的藤黄素结合口袋，对于通过抑制PDEδ与K-Ras的结合以及通过改变其定位导致细胞死亡或抑制增殖而对癌症的预防和治疗是有用的。
• Derivatives of terbutylphenyl-1-amino-4-hydroxybutane their preparation
  申请人：Laboratoire Theramex S.A.

  公开号：US05461059A1

  公开（公告）日：1995-10-24

  ##STR1## The present invention concerns (4-substituted phenyl)4-oxy 1-aminobutane of the general formula (I) in which X is a nitrogen atom or >CH--CH, and R is a cyclic substituent chosen from the group comprising a) a xanthic substituent, b) a benzimidazolic substituent, as well as salts and optic isomers of the compounds of formula (I). The invention also concerns processes for obtaining the compounds of formula (I) and pharmaceutical compositions containing, as antihistamine ingredient, at least one compound of formula (I) or one of its salts with a mineral or organic acid.

  本发明涉及一般式（I）中的（4-取代苯基）4-氧基-1-氨基丁烷，其中X是氮原子或>CH-CH，R是从包括a）黄色素取代基，b）苯并咪唑取代基的群体中选择的环状取代基，以及公式（I）化合物的盐和光学异构体。本发明还涉及获得公式（I）化合物的过程和含有至少一种公式（I）化合物或其与矿物酸或有机酸盐的药物组合物，作为抗组胺剂成分的制药组合物。
• New 2-piperazinylbenzimidazole derivatives
  申请人：FABRICA ESPANOLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A. (FAES)

  公开号：EP0512939A1

  公开（公告）日：1992-11-11

  A description of new 2-piperazinylbenzimidazole derivatives, of general formula where R can be a hydrogen atom, a short chain alkyl group and a phenyl radical, substituted in position four by a halogen, and R₁ can be a hydrogen atom, an alkoxycarbonyl radical, a hydroxymetyl group and a diphenylmethyl group, and their addition salts with pharmaceutically acceptable acids. these compounds are pharmacologically active as antagonists of serotonin 5HT₃ receptors.

  描述通式为 2-哌嗪基苯并咪唑的新衍生物 其中 R 可以是氢原子、短链烷基和苯基，在第四位被卤素取代，R₁ 可以是氢原子、烷氧羰基、羟甲基和二苯基甲基，以及它们与药学上可接受的酸的加成盐。 这些化合物作为血清素 5HT₃ 受体的拮抗剂具有药理活性。
• Chloroquine–astemizole hybrids with potent in vitro and in vivo antiplasmodial activity
  作者：Chitalu C. Musonda、Gavin A. Whitlock、Michael J. Witty、Reto Brun、Marcel Kaiser

  DOI：10.1016/j.bmcl.2008.11.047

  日期：2009.1

  A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds 5-8 possessed improved in vitro activity against a CQ-resistant strain of Plasmodium falciparum, and examples 7 and 8 were active in vivo in mouse models of malaria. (C) 2008 Elsevier Ltd. All rights reserved.
• 5-HT3R Binding of lerisetron: an interdisciplinary approach to drug–Receptor interactions
  作者：Harish S. Parihar、Asha Suryanarayanan、Chun Ma、Prasad Joshi、Padma Venkataraman、Marvin K. Schulte、Karen S. Kirschbaum

  DOI：10.1016/s0960-894x(01)00417-6

  日期：2001.8

  The design, synthesis, and use of lerisetron-based molecular probes to investigate the 5-HT3R binding site are described. A SAR study, which involved distance and electronic parameter modifications of lerisetron's N-benzyl group, resulted in the discovery of a partial agonist. (C) 2001 Elsevier Science Ltd. All rights reserved.