1-(2-(1-methylpiperidin-2-yl)ethyl)-1H-benzo[d]imidazole

• 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: 1-(2-(1-methylpiperidin-2-yl)ethyl)-1H-benzo[d]imidazole
• 英文别名: 1-[2-(1-Methylpiperidin-2-yl)ethyl]benzimidazole；1-[2-(1-methylpiperidin-2-yl)ethyl]benzimidazole
• 化学式: C₁₅H₂₁N₃
• 分子量: 243.352
• InChiKey: XRSDXBYSJFQJIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.533
• 拓扑面积：
  21.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  t-butyl 2-(2-bromoethyl)piperidine-1-carboxylate 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.83h， 生成 1-(2-(1-methylpiperidin-2-yl)ethyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis

  摘要：

  The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.12.042

文献信息

• Rational Design and Synthesis of Thioridazine Analogues as Enhancers of the Antituberculosis Therapy
  作者：Marco Pieroni、Diana Machado、Elisa Azzali、Sofia Santos Costa、Isabel Couto、Gabriele Costantino、Miguel Viveiros

  DOI：10.1021/acs.jmedchem.5b00428

  日期：2015.8.13

  Tuberculosis, caused by Mycobacterium tuberculosis, is still one of the leading infectious diseases globally. Therefore, novel approaches are needed to face this disease. Efflux pumps are known to contribute to the emergence of M tuberculosis drug resistance. Thioridazine has shown good anti-TB properties both in vitro and in vivo, likely due to its capacity to inhibit efflux mechanisms. Here we report the design and synthesis of a number of putative efflux inhibitors inspired by the structure of thioridazine. Compounds were evaluated for their in vitro and ex vivo activity against M. tuberculosis H37Rv. Compared to the parent molecule, some of the compounds synthesized showed higher efflux inhibitory capacity, less cytotoxicity, and a remarkable synergistic effect with anti-TB drugs both in vitro and in human macrophages, demonstrating their potential to be used as coadjuvants for the treatment of tuberculosis.
• A combined ligand- and structure-based approach for the identification of rilmenidine-derived compounds which synergize the antitumor effects of doxorubicin
  作者：Jelica Vucicevic、Tatjana Srdic-Rajic、Marco Pieroni、Jonne M.M. Laurila、Vladimir Perovic、Sabrina Tassini、Elisa Azzali、Gabriele Costantino、Sanja Glisic、Danica Agbaba、Mika Scheinin、Katarina Nikolic、Marco Radi、Nevena Veljkovic

  DOI：10.1016/j.bmc.2016.05.043

  日期：2016.7

  The clonidine-like central antihypertensive agent rilmenidine, which has high affinity for I-1-type imidazoline receptors (I-1-IR) was recently found to have cytotoxic effects on cultured cancer cell lines. However, due to its pharmacological effects resulting also from alpha(2)-adrenoceptor activation, rilmenidine cannot be considered a suitable anticancer drug candidate. Here, we report the identification of novel rilmenidine- derived compounds with anticancer potential and devoid of alpha(2)-adrenoceptor effects by means of ligand-and structure-based drug design approaches. Starting from a large virtual library, eleven compounds were selected, synthesized and submitted to biological evaluation. The most active compound 5 exhibited a cytotoxic profile similar to that of rilmenidine, but without appreciable affinity to alpha(2)-adrenoceptors. In addition, compound 5 significantly enhanced the apoptotic response to doxorubicin, and may thus represent an important tool for the development of better adjuvant chemotherapeutic strategies for doxorubicin-insensitive cancers. (C) 2016 Elsevier Ltd. All rights reserved.
• Synthesis and SAR evaluation of novel thioridazine derivatives active against drug-resistant tuberculosis
  作者：Nicolò Scalacci、Alistair K. Brown、Fernando R. Pavan、Camila M. Ribeiro、Fabrizio Manetti、Sanjib Bhakta、Arundhati Maitra、Darren L. Smith、Elena Petricci、Daniele Castagnolo

  DOI：10.1016/j.ejmech.2016.12.042

  日期：2017.2

  The neuroleptic drug thioridazine has been recently repositioned as possible anti-tubercular drug. Thioridazine showed anti-tubercular activity against drug resistant mycobacteria but it is endowed with adverse side effects. A small library of thioridazine derivatives has been designed through the replacement of the piperidine and phenothiazine moieties, with the aim to improve the anti-tubercular activity and to reduce the cytotoxic effects. Among the resulting compounds, the indole derivative 12e showed an antimycobacterial activity significantly better than thioridazine and a cytotoxicity 15-fold lower. (C) 2016 Elsevier Masson SAS. All rights reserved.