2,4-dinitro-5-(piperidin-1-yl)aniline | 897544-63-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4-dinitro-5-(piperidin-1-yl)aniline
• 英文别名: 1-amino-2,4-dinitro-5-piperidinobenzene；2,4-dinitro-5-piperidin-1-ylaniline
• CAS: 897544-63-7
• 化学式: C₁₁H₁₄N₄O₄
• mdl: MFCD07626348
• 分子量: 266.257
• InChiKey: ZPSOJOFPFHVPBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,4-dinitro-5-(piperidin-1-yl)aniline 在 sodium hydrogensulfide 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 6-nitro-5-(piperidin-1-yl)-1H-benzimidazole-2-thiol
  参考文献：
  名称：

  A reverse method for diversity introduction of benzimidazole to synthesize H+/K+-ATP enzyme inhibitors

  摘要：

  A series of 2-[(2-pyridylmethyl)sulfinyl]benzimidazole derivatives were synthesized via a solution phase synthetic route using a reversal method of diversity introduction. Using this synthetic strategy, we obtained two key intermediates (4-A and 4-B) simultaneously, which allows us to introduce diversity points onto the benzimidazole part of the final product under reliable reaction conditions to identify potent H+/K+-ATP enzyme inhibitors. Compound 141 (IC50 = 1.6 x 10 (5) M) was comparable with H+/K+-ATP enzyme inhibitor in vitro. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.080
• 作为产物：
  描述：

  1,5-二氟-2,4-二硝基苯 在 氨 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 5.5h， 生成 2,4-dinitro-5-(piperidin-1-yl)aniline
  参考文献：
  名称：

  A reverse method for diversity introduction of benzimidazole to synthesize H+/K+-ATP enzyme inhibitors

  摘要：

  A series of 2-[(2-pyridylmethyl)sulfinyl]benzimidazole derivatives were synthesized via a solution phase synthetic route using a reversal method of diversity introduction. Using this synthetic strategy, we obtained two key intermediates (4-A and 4-B) simultaneously, which allows us to introduce diversity points onto the benzimidazole part of the final product under reliable reaction conditions to identify potent H+/K+-ATP enzyme inhibitors. Compound 141 (IC50 = 1.6 x 10 (5) M) was comparable with H+/K+-ATP enzyme inhibitor in vitro. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.080

文献信息

• Novel Trisubstituted Benzimidazoles, Targeting <i>Mtb</i> FtsZ, as a New Class of Antitubercular Agents
  作者：Kunal Kumar、Divya Awasthi、Seung-Yub Lee、Ilaria Zanardi、Bela Ruzsicska、Susan Knudson、Peter J. Tonge、Richard A. Slayden、Iwao Ojima

  DOI：10.1021/jm1012006

  日期：2011.1.13

  GTPase activity of Mtb FtsZ. The result strongly suggests that the increased GTPase activity destabilizes FtsZ assembly, leading to efficient inhibition of FtsZ polymerization and filament formation. The TEM and SEM analyses of Mtb FtsZ and Mtb cells, respectively, treated with a lead compound strongly suggest that lead benzimidazoles have a novel mechanism of action on the inhibition of Mtb FtsZ assembly

  通过合理的药物设计创建了新型三取代苯并咪唑文库。大量这些苯并咪唑表现出有希望的 MIC 值在 0.5-6 μg/mL (2-15 μM) 范围内，因为它们对Mtb H37Rv 菌株具有抗菌活性。此外，五种先导化合物还对具有不同耐药性的临床Mtb菌株表现出优异的活性。所有先导化合物对 Vero 细胞均未表现出明显的细胞毒性（IC 50 > 200 μM），其以剂量依赖性方式抑制Mtb FtsZ 组装。这两种先导化合物出人意料地显示出Mtb的 GTPase 活性增强FtsZ。结果强烈表明，增加的 GTPase 活性使 FtsZ 组装不稳定，从而有效抑制 FtsZ 聚合和细丝形成。分别用先导化合物处理的Mtb FtsZ 和Mtb细胞的 TEM 和 SEM 分析强烈表明，苯并咪唑铅对抑制Mtb FtsZ 组装和 Z 环形成具有新的作用机制。
• BENZIMIDAZOLES AND PHARMACEUTICAL COMPOSITIONS THEREOF
  申请人：Ojima Iwao

  公开号：US20100256203A1

  公开（公告）日：2010-10-07

  The present invention relates to novel benzimidazole derivatives and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to methods of treating a patient infected by Mycobacterium tuberculosis or Francisella tulerensis by administering to the patient a benzimidazole derivative or a pharmaceutically acceptable salt thereof.

  本发明涉及新型苯并咪唑衍生物及其药学上可接受的盐。本发明的另一方面涉及通过向患者给予苯并咪唑衍生物或其药学上可接受的盐来治疗Mycobacterium tuberculosis或Francisella tulerensis感染的患者的方法。
• Benzimidazole-based antibacterial agents against Francisella tularensis
  作者：Kunal Kumar、Divya Awasthi、Seung-Yub Lee、Jason E. Cummings、Susan E. Knudson、Richard A. Slayden、Iwao Ojima

  DOI：10.1016/j.bmc.2013.02.059

  日期：2013.6

  Francisella tularensis is a highly virulent pathogenic bacterium. In order to identify novel potential antibacterial agents against F. tularensis, libraries of trisubstituted benzimidazoles were screened against F. tularensis LVS strain. In a preliminary screening assay, remarkably, 23 of 2,5,6- and 2,5,7-trisubstituted benzimidazoles showed excellent activity exhibiting greater than 90% growth inhibition at 1 mu g/mL. Among those hits, 21 compounds showed MIC90 values in the range of 0.35-48.6 mu g/mL after accurate MIC determination. In ex vivo efficacy assays, four of these compounds exhibited 2-3 log reduction in colony forming units (CFU) per mL at concentrations of 10 and 50 mu g/mL. (C) 2013 Elsevier Ltd. All rights reserved.
• US8232410B2
  申请人：——

  公开号：US8232410B2

  公开（公告）日：2012-07-31
• [EN] BENZIMIDAZOLES AND PHARMACEUTICAL COMPOSITIONS THEREOF<br/>[FR] BENZIMIDAZOLES ET COMPOSITIONS PHARMACEUTIQUES DE CEUX-CI
  申请人：UNIV NEW YORK STATE RES FOUND

  公开号：WO2008130669A1

  公开（公告）日：2008-10-30

  [EN] The present invention relates to novel benzimidazole derivatives and pharmaceutically acceptable salts thereof. Another aspect of the invention relates to methods of treating a patient infected by Mycobacterium tuberculosis or Francisella tulerensis by administering to the patient a benzimidazole derivative or a pharmaceutically acceptable salt thereof.
  [FR] L'invention concerne de nouveaux dérivés du benzimidazole et des sels pharmaceutiquement acceptables de ceux-ci. Un autre aspect de l'invention concerne des procédés de traitement d'un patient infecté par Mycobacterium tuberculosis ou Francisella tulerensis par l'administration au patient d'un dérivé du benzimidazole ou d'un sel pharmaceutiquement acceptable de celui-ci.